COVID-19 vaccine clinical research

Last updated

COVID-19 vaccine clinical research is the clinical research on COVID-19 vaccines, including their efficacy, effectiveness and safety. There are 24 vaccines authorized for use by national governments, with six vaccines being approved for emergency or full use by at least one WHO-recognised stringent regulatory authority; and five of them are in Phase IV. 204 vaccines under clinical trials that have not yet been authorized. There are also nine clinical trials on heterologous vaccination courses.

Contents

In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. Twenty vaccines are authorized by at least one national regulatory authority for public use: one DNA vaccine (ZyCoV-D) two RNA vaccines (Pfizer–BioNTech and Moderna), ten conventional inactivated vaccines (BBIBP-CorV, Chinese Academy of Medical Sciences, CoronaVac, Covaxin, CoviVac, COVIran Barekat, FAKHRAVAC, Minhai-Kangtai, QazVac, and WIBP-CorV), five viral vector vaccines (Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Janssen), and six subunit vaccines (Abdala, COVAX-19, EpiVacCorona, MVC-COV1901, Soberana 02, and ZF2001). [1] [2] In total, 330 vaccine candidates are in various stages of development, with 102 in clinical research, including 30 in Phase I trials, 30 in Phase I–II trials, 25 in Phase III trials, and 8 in Phase IV development. [1]

Formulation

As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity. [3] An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen, such as the COVID‑19 virus or influenza virus. [4] Specifically, an adjuvant may be used in formulating a COVID‑19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID‑19 infection in vaccinated individuals. [4] [5] Adjuvants used in COVID‑19 vaccine formulation may be particularly effective for technologies using the inactivated COVID‑19 virus and recombinant protein-based or vector-based vaccines. Aluminum salts, known as "alum", were the first adjuvant used for licensed vaccines, and are the adjuvant of choice in some 80% of adjuvanted vaccines. [5] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines. [4] [5]

Trial and authorization status

Phase I trials test primarily for safety and preliminary dosing in a few dozen healthy subjects, while Phase II trials following success in Phase I evaluate immunogenicity, dose levels (efficacy based on biomarkers) and adverse effects of the candidate vaccine, typically in hundreds of people. [6] [7] A Phase I–II trial consists of preliminary safety and immunogenicity testing, is typically randomized, placebo-controlled, while determining more precise, effective doses. [7] Phase III trials typically involve more participants at multiple sites, include a control group, and test effectiveness of the vaccine to prevent the disease (an "interventional" or "pivotal" trial), while monitoring for adverse effects at the optimal dose. [6] [7] Definition of vaccine safety, efficacy, and clinical endpoints in a Phase III trial may vary between the trials of different companies, such as defining the degree of side effects, infection or amount of transmission, and whether the vaccine prevents moderate or severe COVID‑19 infection. [8] [9] [10]

A clinical trial design in progress may be modified as an "adaptive design" if accumulating data in the trial provide early insights about positive or negative efficacy of the treatment. [11] [12] Adaptive designs within ongoing Phase II–III clinical trials on candidate vaccines may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, avoiding duplication of research efforts, and enhancing coordination of design changes for the Solidarity trial across its international locations. [11] [13]

List of authorized and approved vaccines

National regulatory authorities have granted emergency use authorizations for twenty-two vaccines. Six of those have been approved for emergency or full use by at least one WHO-recognized stringent regulatory authority. Biologic License Applications for the Pfizer–BioNTech and Moderna COVID‑19 vaccines have been submitted to the US Food and Drug Administration (FDA). [14] [15]

The table below shows various vaccines authorized either for full or emergency use so far, with various other details.

COVID-19 vaccines authorized for emergency use or approved for full use
COVID-19 vaccines authorized for emergency use or approved for full use ()
Vaccine, developers/sponsorsCountry of origin Type (technology)Doses, intervalStorage temperaturePre-marketing study (participants) Postmarketing study (participants)Authorization
Oxford–AstraZeneca COVID-19 vaccine (Vaxzevria, Covishield) [16] [lower-alpha 1] [lower-alpha 2] [20] [21] [22]
University of Oxford, AstraZeneca, CEPI
United Kingdom, Sweden Adenovirus vector (ChAdOx1) [20] 2 doses
4–12 weeks [23]
2–8 °C [24] Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity. [25]
Overall efficacy of 76% after the first dose and 81% after a second dose taken 12 weeks or more after the first. [26]
May 2020 Aug 2021, Brazil (5,000), [27] United Kingdom, India [28]
Phase IV (10,000) [29]
Interventional, non-randomized
Feb 2021 Dec 2024, Denmark
Full (3)
Emergency (172)
Pfizer–BioNTech COVID-19 vaccine (Comirnaty) [30] [31] [32]
BioNTech, Pfizer
Germany, United States RNA (modRNA in lipid nanoparticles) [30] 2 doses
3–4 weeks [33] [lower-alpha 3]
−70±10 °C [lower-alpha 4]
(ULT)
Phase III (43,998)
Randomized, placebo-controlled.
Positive results from an interim analysis were announced on 18 November 2020 [38] and published on 10 December 2020 reporting an overall efficacy of 95%. [39] [40]
Jul–Nov 2020, [41] [42] Germany, United States
Phase IV (10,000) [29]
Interventional, non-randomized
Feb 2021 Dec 2024, Denmark
Full (10)
Emergency (121)
Moderna COVID-19 vaccine (Spikevax) [43] [44]
Moderna, NIAID, BARDA, CEPI
United States RNA (modRNA in lipid nanoparticles) [45] 2 doses
4 weeks [46] [lower-alpha 3]
−20±5 °C [47]
(freezer)
Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity.
Positive results from an interim analysis were announced on 15 November 2020 [48] and published on 30 December 2020 reporting an overall efficacy of 94%. [49]
Jul 2020 Oct 2022, United States
Phase IV (10,000) [29]
Interventional, non-randomized
Feb 2021 Dec 2024, Denmark
Full (4)
Emergency (97)
Janssen COVID-19 vaccine [50] [51]
Janssen Vaccines (Johnson & Johnson), BIDMC
United States, Netherlands Adenovirus vector (recombinant Ad26) [52] 1 dose [53] 2–8 °C [53] Phase III (40,000)
Randomized, double-blinded, placebo-controlled
Positive results from an interim analysis were announced on 29 January 2021. J&J reports an efficacy of 66% against mild and moderate symptoms, and 85% against severe symptoms. Further, the mild and moderate efficacy ranged from 64% in South Africa to 72% in the United States. [54] [55]
Jul 2020 ? 2023, United States, Argentina, Brazil, Chile, Colombia, Mexico, Peru, the Philippines, South Africa, Ukraine
Full (2)
Emergency (105)
Sinopharm BIBP COVID-19 vaccine [56]
Sinopharm: Beijing Institute of Biological Products
China Inactivated SARS‑CoV‑2 (vero cells) [56] 2 doses
3–4 weeks [57]
2–8 °C [58] Phase III (48,000)
Randomized, double-blind, parallel placebo-controlled, to evaluate safety and protective efficacy.
Peer-reviewed results indicate 78.1% efficacy against symptomatic COVID-19. [59]
Jul 2020 Jul 2021, United Arab Emirates, Bahrain, Jordan, [60] Argentina, [61] Morocco, [62] Peru [63]
Full (4)
Emergency (93)
Sputnik V COVID-19 vaccine (Gam-COVID-Vac)
Gamaleya Research Institute of Epidemiology and Microbiology
Russia Adenovirus vector (recombinant Ad5 and Ad26) [64] 2 doses
3 weeks [65]
−18 °C [lower-alpha 5]
(freezer)
Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety. [67]
Interim analysis from the trial was published in The Lancet , indicating 91.6% efficacy without unusual side effects. [68]
Aug 2020 May 2021, Russia, Belarus, [69] India, [70] [71] Venezuela, [72] United Arab Emirates [73]
Full (2)
Emergency (75)
CoronaVac [74] [75] [76]
Sinovac
China Inactivated SARS‑CoV‑2 (vero cells) [74] 2 doses
2–4 weeks [77]
2–8 °C [78] Phase III (33,620)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
Peer-reviewed Phase III results from Turkey showed an efficacy of 83.5%. [79] A Chilean study showed 65% efficacy against symptomatic cases, 87% against hospitalization, 90% against ICU admissions, and 86% against deaths. [80] [81] Brazil announced results showing 50.7% effective at preventing symptomatic infections, 83.7% effective in preventing mild cases, and 100% effective in preventing severe cases. [82]
July 2020 Oct 2021, Brazil (15,000); [83] Aug 2020 January 2021, Indonesia (1,620); Oct Nov 2020, China (1,040); [84] Nov 2020 Jan 2022, [85] Chile (3,000); [86] Apr 2021 Jun 2022, the Philippines (phase II/III: 352); [87] Sep 2020 Feb 2021, Turkey (13,000); [88]
Phase IV (37,867) [89] [90]
Interventional
Feb 2021 Feb 2022, Serrana (São Paulo) (27,711); Mar 2021 Mar 2022, Manaus (10,156)
Full (1)
Emergency (64)
Covaxin
Bharat Biotech, Indian Council of Medical Research
India Inactivated SARS‑CoV‑2 (vero cells) [91] 2 doses
4 weeks [92]
2–8 °C [92] Phase III (25,800)
Randomised, observer-blinded, placebo-controlled [93]
Bharat Biotech reported an interim efficacy is 78% for its phase 3 trial. [94]
Nov 2020 Mar 2021, India.
Phase IV (1,000) [95]
Interventional, non-randomized
July 2021 Dec 2021, India
Full (0)
Emergency (21)
Sputnik Light
Gamaleya Research Institute of Epidemiology and Microbiology [96]
Russia Adenovirus vector (recombinant Ad26) [97] 1 dose [97] 2–8 °C [98] Phase III (7,000) [99]
Randomised, double-blind, placebo-controlled trial [97]
Feb  Dec 2021, Russia (6,000)
Full (0)
Emergency (16)
Convidecia
CanSino Biologics, Beijing Institute of Biotechnology of the Academy of Military Medical Sciences
China Adenovirus vector (recombinant Ad5) [100] 1 dose [101] 2–8 °C [101] Phase III (40,000)
Global multi-center, randomized, double-blind, placebo-controlled to evaluate efficacy, safety and immunogenicity.
In February 2021, interim analysis from global trials showed an efficacy of 65.7% against symptomatic cases of COVID-19 and 90.98% efficacy against severe cases. [101]
Mar–Dec 2020, China; Sep 2020 Dec 2021, Pakistan; Sep–Nov 2020, Russia, [102] China, Argentina, Chile; [103] Mexico; [104] Pakistan; [105] Saudi Arabia [106] [107]
Full (1)
Emergency (9)
Sinopharm WIBP COVID-19 vaccine
Sinopharm: Wuhan Institute of Biological Products
China Inactivated SARS‑CoV‑2 (vero cells)2 doses
3 weeks [108] [109] [110]
2–8 °CPhase III (51,600)
Randomized, double-blind, placebo-controlled [111]
Peer-reviewed results indicate 72.8% efficacy against symptomatic COVID-19. [59]
Jul 2020 Mar 2021, Bahrain, Egypt, Jordan, United Arab Emirates; [108] Sep 2020 Sep 2021, Peru; [109] Sep 2020 Dec 2020, Morocco [112]
Full (1)
Emergency (5)
EpiVacCorona [113] [114]
Vector Institute
Russia Subunit (peptide) [113] 2 doses
3 weeks [113]
2–8 °C [115] Phase III (40,150(planned), 3,000(started)) [116]
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety
Nov 2020 Dec 2021, Russia (3,000) [117] [118] [119] [120]
Full (1)
Emergency (2)
ZF2001 (ZIFIVAX) [121]
Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.
China Subunit (recombinant)3 doses
30 days [122] [123]
2–8 °C [124] Phase III (29,000)
Randomized, double-blind, placebo-controlled [122]
Dec 2020 Apr 2022, China, Ecuador, Indonesia, Malaysia, Pakistan, Uzbekistan [125] [126]
Full (0)
Emergency (3)
Abdala
BioCubaFarma, Center for Genetic Engineering and Biotechnology
Cuba Subunit 3 doses
2 weeks [127]
2–8 °C [128] Phase III (48,290) [129]
Multicenter, randomized, double-blind, placebo-controlled. [127]
Mar–Jul 2021, Cuba
Full (0)
Emergency (4)
CoviVac [130]
The Chumakov Centre at the Russian Academy of Sciences
Russia Inactivated SARS‑CoV‑2 (vero cells) [131] 2 doses
2 weeks [132]
2–8 °C [132] Phase III (32,000) [133]
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
May 2021 ?, Russia (3,000) [134]
Full (0)
Emergency (1)
QazCovid-in (QazVac) [135]
Research Institute for Biological Safety Problems
Kazakhstan Inactivated SARS‑CoV‑2 2 doses
3 weeks [136]
2–8 °C [137] Phase III (3,000)
Randomised, blind, placebo-controlled trial [138]
Mar 2021 Jul 2021, Kazakhstan [138]
Full (0)
Emergency (2)
Minhai COVID-19 vaccine (KCONVAC)
Minhai Biotechnology Co., Shenzhen Kangtai Biological Products
China Inactivated SARS‑CoV‑2 (vero cell)2 doses
4 weeks [139]
2–8 °CPhase III (28,000) [139]
Multi-national, Randomized, Double-blind, Placebo-controlled.
April–Nov 2021, China, Malaysia, the Philippines
Full (0)
Emergency (1)
COVIran Barekat (COVIRAN) [140]
Barkat Pharmaceutical Group, Shifa Pharmed Industrial Group
Iran Inactivated SARS‑CoV‑2 2 doses
4 weeks [141]
2–8 °C [142] Phase III (20,000) [141]
Randomized, double-blind, parallel arms, placebo-controlled.
Mar–Jun 2021, Iran
Full (0)
Emergency (1)
FAKHRAVAC [143] (MIVAC) [144]
Organization of Defensive Innovation and Research
Iran Inactivated SARS‑CoV‑2 2 doses
3 weeks [145]
2–8 °CPhase III (41,128)
Randomized, double blind, parallel design, non-inferiority design, compared to Sinopharm vaccine. [145]
Sep–Nov 2021, Iran
Full (0)
Emergency (1)
Chinese Academy of Medical Sciences COVID-19 vaccine (Covidful) [146] [147]
Chinese Academy of Medical Sciences, Institute of Medical Biology
China Inactivated SARS‑CoV‑2 2 doses
2 weeks [147]
2–8 °CPhase III (34,020)
Randomized, double-blinded, single-center, placebo-controlled
Jan–Sep 2021, Brazil, Malaysia
Full (0)
Emergency (1)
Soberana 02 (FINLAY-FR-2, Pasteurcovac [148] )
BioCubaFarma, Instituto Finlay de Vacunas
Cuba, Iran Subunit (conjugate)2 doses
4 weeks [149]
2–8 °C [128] Phase III (68,010) [150] [149] [151]
Cuba (44,010): Multicenter, adaptive, parallel-group, randomized, placebo-controlled, double-blind.
Iran (24,000): Double-blind, randomized, placebo-controlled
Mar–May 2021, Cuba, Iran, Venezuela [152] [ unreliable source? ]
Full (0)
Emergency (3)
MVC COVID-19 vaccine (MVC-COV1901)
Medigen Vaccine Biologics, Dynavax Technologies [153]
Taiwan Subunit (S-2P protein +CpG 1018)2 doses
4 weeks [154]
2–8 °C [155] Phase III (5,120) [156] [157] [158]
Phase IIa (3,700): Prospective, double-blinded, multi-center, multi-regional.
Phase IIb (400): Prospective, randomized, double-blind, dose-comparison, multi-center.
Phase III (1,020): Parallel group, prospective, randomized, double-blind, active-controlled, two-arm, multi-center. [159]
Dec 2020 Dec 2021, Paraguay (phase III), [160] Taiwan (phase II), Vietnam (phase IIa)
Full (0)
Emergency (1)
ZyCoV-D [161]
Cadila Healthcare,
Biotechnology Industry Research Assistance Council
India DNA (plasmid expressing SARS‑CoV‑2 S protein)3 doses
4 weeks [161] [162]
2–8 °C [163] Phase III (30,000) [164] [165]
Randomised, blind, placebo-controlled trial [166]
Jan–May 2021, India [167]
Full (0)
Emergency (1)
COVAX-19 (SpikoGen) [168]
Vaxine Pty Ltd, [169] Cinnagen [170]
Australia, Iran Subunit (recombinant protein)2–8 °CPhase III (16,876) [171]
Randomized, Two-armed, Double-blind, Placebo controlled
Aug Sep 2021, Iran
Full (0)
Emergency (1)
  1. Serum Institute of India will be producing the ChAdOx1 nCoV-19 vaccine for India [17] and other low- and middle-income countries. [18]
  2. Oxford name: ChAdOx1 nCoV-19. Manufacturing in Brazil to be carried out by Oswaldo Cruz Foundation. [19]
  3. 1 2 Recommended interval. The second dose of the Pfizer–BioNTech and Moderna vaccines can be administered up to six weeks after the first dose to alleviate a shortage of supplies. [34] [35]
  4. Long-term storage temperature. The Pfizer–BioNTech COVID-19 vaccine can be kept between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use, and between 2 and 8 °C (36 and 46 °F) for up to five days before use. [36] [37]
  5. Storage temperature for the frozen Gam-COVID-Vac formulation. The lyophilised Gam-COVID-Vac-Lyo formulation can be stored at 2-8°C. [66]

Vaccine candidates in human trials

The table below shows various vaccine candidates and the phases which they have completes so far. Current phases are also shown along with other details.

COVID‑19 candidate vaccines in Phase I–III trials
COVID‑19 vaccine candidates in Phase I–III trials [172] [173] [174]
()
Vaccine candidates,
developers, and sponsors
Country of origin Type (technology)Current phase (participants)
design
Completed phase [lower-alpha 1] (participants)
Immune response
Pending authorization
Novavax COVID-19 vaccine (Covovax) [175] [176]
Novavax, CEPI
United States Subunit [177] [178] [179] /virus-like particle [180] [181] (SARS‑CoV‑2 recombinant spike protein nanoparticle with adjuvant)Phase III (49,600)
Randomised, observer-blinded, placebo-controlled trial [182]
Sep 2020 Jan 2021, UK (15,000); Dec 2020 Jun 2023, US, Mexico, Puerto Rico (33,000); [183] India (Phase II/III: 1,600) [184] [185]
Phase I–II (131)
IgG and neutralizing antibody response with adjuvant after booster dose. [186]
Emergency (12)
Sanofi–GSK COVID-19 vaccine (VAT00008, Vidprevtyn)
Sanofi Pasteur, GSK
France, United Kingdom Subunit (SARS-CoV-2 S adjuvanted recombinant protein)Phase III (37,430) [199] [200]
A Parallel-group, Phase III, Multi-stage, Modified Double-blind, Multi-armed Study to Assess the Efficacy, Safety, and Immunogenicity of Two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (Monovalent and Bivalent) for Prevention Against COVID-19 in Adults 18 Years of Age and Older.
May 2021 Jan 2023, Colombia, Dominican Republic, Ghana, Honduras, India (3,000), Japan, Kenya, [201] Mexico, [202] Nigeria, Pakistan, Sri Lanka, Uganda, United States
Phase I–II (1,160)
Phase I-IIa (440): Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine Formulations (With or Without Adjuvant) in Healthy Adults 18 Years of Age and Older. [203]
Phase IIb (720): Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine With AS03 Adjuvant in Adults 18 Years of Age and Older. [204]
Sep 2020 Apr 2022, United States
Emergency (4)
CoVLP [209] [210]
Medicago, GSK
Canada, United Kingdom Virus-like particles [lower-alpha 2] (recombinant, plant-based with AS03)Phase III (30,918)
Event-driven, randomized, observer blinded, placebo-controlled [212]
Nov 2020 Dec 2021, Brazil, Canada, United Kingdom, United States
Phase I (180)
Neutralizing antibodies at day 42 after the first injection (day 21 after the second injection) were at levels 10x that of COVID-19 survivors.
Jul 2020 Sept 2021, Canada [213]
Emergency (1)
Valneva COVID-19 vaccine [215] [ unreliable source? ] [216]
Valneva
France Inactivated SARS‑CoV‑2 Phase III (4,769) [217] [218] [219]
Phase III (4,019+750): Randomized, observer-blind, controlled, non-inferiority.
Apr–Dec 2021, New Zealand, United Kingdom
Phase I–II (3,039)
Phase I/II (153): Randomized, multi-center, double-blinded.
Phase II (2,886): A randomised, phase II UK multi-centre study to determine reactogenicity and immunogenicity of booster vaccination against ancestral and novel variants of SARS-CoV-2. [220]
Dec 2020 Jun 2021, United Kingdom
Emergency (2)
Nanocovax [223]
Nanogen Pharmaceutical Biotechnology JSC
Vietnam Subunit (SARS‑CoV‑2 recombinant spike protein with aluminum adjuvant) [224] [225] Phase III (13,000) [226] [227]
Adaptive, multicenter, randomized, double-blind, placebo-controlled
Jun 2021 Jul 2022, Vietnam
Phase I–II (620) [228]
Phase I (60): Open label, dose escalation.
Phase II (560): Randomization, double-blind, multicenter, placebo-controlled.
Dec 2020 Jun 2021, Vietnam
Emergency (1)
UB-612
United Biomedical,Inc, Vaxxinity, DASA
Brazil, United States Subunit (Multitope peptide based S1-RBD-protein based vaccine)Phase III (18,320) [230] [231]
Phase IIb/III (7,320): Randomized, Multicenter, Double-Blind, Placebo Controlled, Dose-Response.
Phase III (11,000)
Jan 2021 Mar 2023, Taiwan (phase 2b/3), India (phase 3) [232]
Phase I–II (3,910) [233]
Phase 1 (60): Open-label study
Phase IIa (3,850): Placebo-controlled, Randomized, Observer-blind Study.
Sep 2020 Jan 2021, Taiwan
Emergency (1)
Razi Cov Pars [235] [236]
Razi Vaccine and Serum Research Institute
Iran Subunit (Recombinant Spike protein)Phase III (41,128) [237]
Two parallel and equal groups, randomized, double blind, non-inferiority design, compared to Sinopharm vaccine.
Sep–Dec 2021, Iran
Phase I–II (633) [238]
Phase I (133): Randomized, double blind, placebo controlled.
Phase II (500): Two parallel groups, randomized, double blind, placebo controlled. [239]
Jan–Jun 2021, Iran
TURKOVAC
Health Institutes of Turkey
Turkey Inactivated SARS‑CoV‑2 Phase III (40,800) [240]
Randomized, double-blinded, multi-center, active-controlled.
Jun 2021 – Sep 2021, Turkey
Phase I–II (294) [241] [242]
Phase I (44): Study for the Determination of Safety and Immunogenicity of Two Different Strengths of the Inactivated COVID-19 Vaccine ERUCOV-VAC, Given Twice Intramuscularly to Healthy Volunteers, in a Placebo Controlled Study Design.
Phase 2 (250): Study for the Determination of Efficacy, Immunogenicity and Safety of Two Different Strengths of the Inactivated COVID-19 Vaccine ERUCOV-VAC, in a Placebo Controlled, Randomized, Double Blind Study Design.
Nov 2020 Apr 2021, Turkey
West China Hospital COVID-19 vaccine
Jiangsu Province Centers for Disease Control and Prevention, West China Hospital (WestVac Biopharma), Sichuan University
China Subunit (recombinant with Sf9 cell)Phase III (40,000) [243]
Multicenter, randomized, double-blind, placebo-controlled.
Jun 2021 Feb 2022, Indonesia, Kenya, Malaysia, [244] Mexico, Nepal, the Philippines (5,000) [245]
Phase I–II (5,128) [246] [247] [248]
Phase I (168): Single-center, Randomized, Placebo-controlled, Double-blind.
Phase IIa (960):Single-center, Randomized, Double-Blinded, Placebo-Controlled.
Phase IIb (4,000):Single-center, Randomized, Double-Blinded, Placebo-Controlled.
Aug 2020 May 2021, China
DelNS1-2019-nCoV-RBD-OPT (DelNS1-nCoV-RBD LAIV)
Beijing Wantai Biological Pharmacy, University of Hong Kong
China, Hong KongReplicating Viral vector (flu-based-RBD[ clarification needed ])Phase III (40,000) [249]
Multi-center, Randomized, Double-blind, Placebo controlled.
Oct 2021 Apr 2022, the Philippines
Phase I–II (895) [250] [251]
Phase I (60+115=175)
Phase II (720)
Sep 2020 Sep 2022, China (60), Hong Kong (115)
Versamune-CoV-2FC  [ pt ]
Farmacore Biotechnology, PDS Biotechnology Corporation, Faculty of Medicine of Ribeirão Preto
Brazil, United States Subunit Phase III (30,000) [252]
Double-blind, randomized controlled.
Aug–Dec 2021, Brazil
Phase I–II (360) [253] [254] [255]
Double-blind, randomized controlled.
Mar–Aug 2021, Brazil
SCB-2019 [256] [257]
Clover Biopharmaceuticals, [258] [259] Dynavax Technologies, [260] CEPI
China Subunit (spike protein trimeric subunit with combined CpG 1018 and aluminium adjuvant)Phase III (29,300)
Phase II/III (29,000): Randomized, double-blind, controlled.
Phase III (300): Double-blind, randomized, controlled. [261]
Mar 2021 Oct 2022, Belgium, Brazil, Colombia, Dominican Republic, Germany, Nepal, Panama, the Philippines, Poland, South Africa, Ukraine
Phase I–II (950)
Phase I (150): Randomized, Double-blind, Placebo-controlled, First-in-human.
Phase II (800): Multi-center, Double-blind, Randomized, Controlled. [262]
Jun 2020 Oct 2021, Australia (phase 1), China (phase 2)
Walvax COVID-19 vaccine (ARCoV) [263]
PLA Academy of Military Science, Walvax Biotech, [264] Suzhou Abogen Biosciences
China RNA Phase III (28,000) [265]
Multi-center, Randomized, Double-blind, Placebo-controlled
May–Nov 2021, China, [266] Colombia, Indonesia, Malaysia, Mexico, Nepal, Pakistan, Turkey
Phase I–II (908)
Phase I (168)
Phase II (420)
Phase I/II (320) [267]
Jun 2020 Oct 2021, China [268]
ARCT-154 (VBC-COV19-154 in Vietnam) [269] [270] [271]
Arcturus Therapeutics, Vinbiocare
United States, Vietnam RNA Phase III (20,600)
Phase IIIa (600): Randomized, double-blinded, placebo controlled.
Phase IIIb (20,000): Randomized, double-blinded, placebo controlled. [272] [273]
Oct-Dec 2021, Vietnam
Phase I–II (400)
Phase I (100): Randomized, double-blinded, placebo controlled.
Phase II (300): Randomized, double-blinded, placebo controlled.
Aug-Oct 2021, Vietnam [274]
ReCOV
Jiangsu Rec-Biotechnology Co Ltd
China Subunit (Recombinant two-component spike and RBD protein (CHO cell))Phase II–III (20,301) [275]
Multi-center, randomized, double-blind, placebo-controlled.
Dec 2021–Dec 2022, China, New Zealand
Phase I (160) [276]
First-in-human, randomized, double-blind, placebo-controlled, dose-finding.
Jun–Dec 2021, New Zealand
Zhongyianke Biotech–Liaoning Maokangyuan Biotech COVID-19 vaccine
Zhongyianke Biotech, Liaoning Maokangyuan Biotech, Academy of Military Medical Sciences
China Subunit (Recombinant)Phase III (14,600) [277]
International multicenter, randomized, double-blind, placebo-controlled.
Sep 2021–?, China
Phase I–II (696) [278]
Phase I (216): Randomized, placebo-controlled, double-blind.
Phase II (480): Single-center, randomized, double blinded, placebo controlled. [279]
Oct 2020 Jul 2021, China
GX-19 (GX-19N) [280] [281] [282]
Genexine consortium, [283] [284] International Vaccine Institute
South Korea DNA Phase II–III (14,000) [285]
Randomized, double-blinded, placebo-controlled.
Oct 2021 Oct 2022, Indonesia, Seoul
Phase I–II (410)
Phase I-II (170+210+30): Multi-center, some open-labeled, some double-blinded, single arm, randomized, placebo-controlled
Jun 2020 Jul 2021, Seoul
GRAd-COV2 [286] [287]
ReiThera, Lazzaro Spallanzani National Institute for Infectious Diseases
Italy Adenovirus vector (modified gorilla adenovirus vector, GRAd)Phase III (10,300) [288] [289]
Randomized, stratified, observer-blind, placebo-controlled.
Mar–Oct 2021, Italy
Phase I (90) [290]
Subjects (two groups: 18–55 and 65–85 years old) randomly receiving one of three escalating doses of GRAd-COV2 or a placebo, then monitored over a 24-week period. 93% of subjects who received GRAd-COV2 developed anti-bodies.
Aug–Dec 2020, Rome
GBP510
SK Bioscience Co. Ltd., GSK
South Korea, United Kingdom Subunit (Recombinant protein nanoparticle with adjuvanted with AS03)Phase III (4,000) [291]
Randomized, active-controlled, observer-blind, parallel-group, multi-center. [292]
Aug 2021-Mar 2022, South Korea
Phase I–II (580) [293] [294]
Phase I-II (260-320): Placebo-controlled, randomized, observer-blinded, dose-finding.
Jan–Aug 2021, South Korea
Unnamed
National Vaccine and Serum Institute, Lanzhou Institute of Biological Products Co., Ltd., Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd., Zhengzhou University
China Inactivated SARS‑CoV‑2 Phase III (3,648) [295] [296]
Phase III (1,800): Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above.
Phase III (1,848):Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above.
Sep 2021 Dec 2023, United Arab Emirates
Phase I–II (3,580) [297]
Phase I/II Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of Recombinant SARS-CoV-2 Vaccine (CHO Cell) in Healthy People Aged 3 Years and Older.
Apr 2021 Oct 2022, China
Bio E COVID-19 (Corbevax) [298] [299] [300]
Biological E. Limited, Baylor College of Medicine, [301] CEPI
India, United States Subunit (using an antigen)Phase III (1,268) [302]
Phase 2b/3: Single Arm, Prospective, multicentre. [303]
Apr Aug 2021, India
Phase I–II (360) [304]
Randomized, Parallel Group Trial
Nov 2020 Feb 2021, India
BriLife (IIBR-100) [305]
The Israel Institute for Biological Research
Israel Vesicular stomatitis vector (recombinant)Phase II–III (20,000) [306]
Randomized, multi-center, placebo-controlled.
Sept Dec 2021, Israel
Phase I–II (1,040) [307]
Randomized, multi-center, placebo-controlled, dose-escalation.
Oct 2020 May 2021, Israel
Inovio COVID-19 Vaccine (INO-4800) [308] [309]
Inovio, CEPI, Korea National Institute of Health, International Vaccine Institute
South Korea, United States DNA vaccine (plasmid delivered by electroporation)Phase II–III (6,578)
Phase II/III (6,578): Randomized, placebo-controlled, multi-center. [310]
Nov 2020 Sep 2022, United States (phase II/III) [lower-alpha 3]
Phase I–II (920)
Phase Ia (120): Open-label trial.
Phase Ib-IIa (160): Dose-Ranging Trial. [311]
Phase II (640): Randomized, double-blinded, placebo-controlled, dose-finding. [312]
April 2020 Feb 2022, China (phase II), South Korea (phase Ib-IIa), United States
HGC019 [313]
Gennova Biopharmaceuticals, HDT Biotech Corporation [314]
India, United States RNA Phase II–III (4,400) [315]
A prospective, multicentre, randomized, active-controlled (with COVISHIELD), observer-blind study to evaluate safety, tolerability and immunogenicity in healthy adults.
Phase II (400)
Phase III (4,000)
Sep 2021 ?, India
Phase I–II (620) [316] [317] [318]
Randomized, phase I/II, placebo-controlled, dose-ranging, parallel-group, crossover, multi-centre study to evaluate the safety, tolerability and immunogenicity in healthy adult subjects.
Phase I (120) open-label study in healthy 18-70 year-olds.
Phase II (500) observer-blind study in healthy 18-75 year-olds.
Apr 2021 Oct 2021, India
LYB001
Patronus Biotech
ChinaPhase II–III (1,900) [319]
Phase II: Randomized, double blinded, placebo-controlled
Phase III: Single-armed, open-label expanded.
Oct 2021 ?, Laos
Phase I (100) [320]
Randomized, double blinded, placebo-controlled.
Dec 2021 Feb 2022, Laos
AG0302-COVID‑19 [321] [322]
AnGes Inc., [323] AMED
Japan DNA vaccine (plasmid)Phase II–III (500)
Randomized, double-blind, placebo controlled [324]
Nov 2020 Apr 2021, Japan
Phase I–II (30)
Randomized/non-randomized, single-center, two doses
Jun–Nov 2020, Osaka
202-CoV
Shanghai Zerun Biotechnology Co., Ltd., Walvax Biotech
China Subunit (Spike protein (CHO cell) 202-CoV with CpG / alum adjuvant)Phase II (1,056) [325]
Randomized, Double-blinded, Placebo-controlled.
July–Dec 2021, China
Phase I (144) [326]
Randomized, double-blinded, placebo-controlled.
July–Dec 2021, China
VXA-CoV2-1(VXA-CoV2-1.1-S)
Vaxart
United States Viral vector Phase II (896) [327]
Double-Blind, Multi-Center, Randomized, Placebo-Controlled, Dose-Ranging.
Oct 2021 Mar 2022, United States
Phase I (83) [328] [329]
Phase Ia (35): Double-blind, randomized, placebo-controlled, first-in-Human.
Phase Ib (48): Multicenter, randomized, double-blind, placebo-controlled.
Sep 2020 Aug 2021, United States
V-01
Livzon Mabpharm, Inc.
China Subunit (SARS-CoV-2 recombinant fusion protein)Phase II (880) [330]
Randomized, double-blind, and placebo-controlled.
Mar–May 2021, China
Phase I (180) [331]
Single-center, randomized, double-blind and placebo-controlled.
Feb–Mar 2021, China
Unnamed
Ningbo Rong’an Biological Pharmaceutical Co., Ltd.
China Inactivated SARS‑CoV‑2 Phase II (600) [332]
Randomized, double-blind, placebo-controlled.
Oct 2021 Mar 2022, China
Phase I (150) [333]
Randomized, double-blind, placebo-controlled.
Aug Oct 2021, China
Unnamed
Tsinghua University, Tianjin Medical University, [334] Walvax Biotech
China Viral vector Phase II (360) [335]
Jul–Nov 2021, China
Phase I (60) [336]
May–Jun 2021, China
Unnamed
Ihsan Gursel, Scientific and Technological Research Council of Turkey
Turkey Virus-like particle Phase II (330) [337]
Randomized, parallel dose assigned, double blind, multi center.
Jun Sep 2021, Turkey
Phase I (36) [338]
double-blinded, randomised, placebo controlled.
Mar May 2021, Turkey
COH04S1
City of Hope Medical Center
United States Viral vector Phase II (240) [339]
Multi-center, observer-blinded, EUA vaccine-controlled, randomized.
Aug 2021 Jun 2023, California
Phase I (129) [340]
Dose Escalation Study.
Dec 2020 Nov 2022, California
ABNCoV2
Bavarian Nordic. [341] Radboud University Nijmegen
Denmark, Netherlands Virus-like particle Phase II (210) [342] [343]
Single center, sequential dose-escalation, open labelled trial.
Aug–Dec 2021, Germany
Phase I (42) [344]
Single center, sequential dose-escalation, open labelled trial.
Mar–Dec 2021, Netherlands
SCB-2020S
Clover Biopharmaceuticals [345]
China Subunit Phase I–II (150) [346]
Randomized, controlled, observer-blind.
Aug 2021 Apr 2022, Australia
Preclinical
SCTV01C
Sinocelltech
China Subunit Phase I–III (20,840) [347] [348]
12420+8420=20840: multicenter, randomized, double-blinded trial.
Aug 2021 May 2022, China
Preclinical
NDV-HXP-S (ButanVac, COVIVAC, HXP-GPOVac, Patria)
Icahn School of Medicine at Mount Sinai, Institute of Vaccines and Medical Biologicals, [349] Butantan Institute, Laboratorio Avimex, National Council of Science and Technology, Mahidol University, University of Texas at Austin
Brazil, Mexico, Thailand, United States, Vietnam Newcastle disease virus (NDV) vector (expressing the spike protein of SARS-CoV-2, with or without the adjuvant CpG 1018)/Inactivated SARS‑CoV‑2 Phase I–II (6,439)
Randomized, placebo-controlled, observer-blind.
Mar 2021 May 2022; Brazil (5,394), Mexico (Phase I: 90), Thailand (460), [350] Vietnam (495) [351] [352]
Preclinical
ARCT-021 [353] [354]
Arcturus Therapeutics, Duke–NUS Medical School
United States, Singapore RNA Phase I–II (798)
Phase I/II (92): Randomized, double-blinded, placebo controlled
Phase II (600): Randomized, observer-blind, placebo-controlled, multiregional, multicenter trial in healthy adults to evaluate the safety, reactogenicity, and immunogenicity. [355]
Phase IIa (106): Open label extension trial to assess the safety and long-term immunogenicity by giving single-dose vaccine to the participants from the parent study that received placebo or were seronegative at screening. [356]
Aug 2020 Apr 2022, Singapore, United States (phase IIa)
Preclinical
Unnamed
PT Bio Farma
Indonesia Subunit Phase I–II (780) [357]
Observer-Blind, Randomized, Controlled.
Oct 2021 Jan 2022, Indonesia
Preclinical
VBI-2902 [358]
Variation Biotechnologies
United States Virus-like particle Phase I–II (780) [359]
Randomized, observer-blind, dose-escalation, placebo-controlled
Mar 2021 Jun 2022, Canada
Preclinical
ICC Vaccine [360]
Novavax
United States Subunit Phase I–II (640) [361]
Randomized, observer-blinded.
Sep 2021 Mar 2022, Australia
Preclinical
EuCorVac-19 [362]
EuBiologics Co
South Korea Subunit (spike protein using the recombinant protein technology and with an adjuvant)Phase I–II (280)
Dose-exploration, randomized, observer-blind, placebo-controlled
Feb 2021 Mar 2022, the Philipppines (phase II), South Korea (phase I/II)
Preclinical
RBD SARS-CoV-2 HBsAg VLP
SpyBiotech
United Kingdom Virus-like particle Phase I–II (280) [363]
Randomized, placebo-controlled, multi-center.
Aug 2020 ?, Australia
Preclinical
AV-COVID-19
AIVITA Biomedical, Inc., Ministry of Health (Indonesia)
United States, IndonesiaDendritic cell vaccine (autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein, with or without GM-CSF)Phase I–II (202) [364] [365]
Adaptive.
Dec 2020 Feb 2022, Indonesia (phase I), United States (phase I/II)
Preclinical
COVID-eVax
Takis Biotech
Italy DNA Phase I–II (160) [366]
Multicenter, open label.
Phase I: First-in-human, dose escalation.
Phase II: single arm or two arms, randomized, dose expansion.
Feb–Sep 2021, Italy
Preclinical
BBV154 [367]
Bharat Biotech [368]
India Adenovirus vector (intranasal)Phase I–II (375) [367] [369]
Phase I (175): Randomized, double-blinded, multicenter.
Phase II (200): Randomized, double blind, multicenter. [370]
Mar 2021–?, India
Preclinical
VB10.2129 and VB10.2210
Vaccibody [371] [372]
Norway DNA Phase I–II (160) [373] [374]
Open Label, Dose Escalation.
Oct 2021–Jun 2022, Norway
Preclinical
ChulaCov19
Chulalongkorn University
Thailand RNA Phase I–II (72) [375]
Phase 1 (72): single-center, dose-escalation, first in human study in 2 age groups: 18-55 years-old and 56-75 years-old.
Phase 2: Multi-center, observer-blinded, placebo-controlled study to assess the safety, reactogenicity, and immunogenicity in healthy adults between 18-75 years old.
May-September 2021, Thailand
Preclinical
COVID‑19/aAPC [376]
Shenzhen Genoimmune Medical Institute [377]
China Lentiviral vector (with minigene modifying aAPCs)Phase I (100) [376]
Single group, open-label study to evaluate safety and immunity.
Feb 2020 Jul 2023, Shenzhen
Preclinical
LV-SMENP-DC [378]
Shenzhen Genoimmune Medical Institute [377]
China Lentiviral vector (with minigene modifying DCs)Phase I–II (100) [378]
Single-group, open label, multi-center study to evaluate safety and efficacy.
Mar 2020 Jul 2023, Shenzhen
Preclinical
ImmunityBio COVID-19 vaccine (hAd5)
ImmunityBio
United States Viral vector Phase I–II (540) [379] [380] [381] [382] [383]
Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of a Subcutaneously- and Orally- Administered Supplemental Spike & Nucleocapsid-targeted COVID-19 Vaccine to Enhance T Cell Based Immunogenicity in Participants Who Have Already Received Prime + Boost Vaccines Authorized For Emergency Use.
Oct 2020  Sep 2021, South Africa, United States
Preclinical
PTX-COVID19-B [384]
Providence Therapeutics
Canada RNA Phase I (60) [384]
First-in-Human, Observer-Blinded, Randomized, Placebo Controlled. [385]
Jan–May 2021, Canada
Preclinical
COVAC-2 [386]
VIDO (University of Saskatchewan)
Canada Subunit (spike protein + SWE adjuvant)Phase I (108) [386]
Randomized, observer-blind, dose-escalation. [387]
Feb 2021 Oct 2022, Halifax
Preclinical
COVI-VAC (CDX-005) [388]
Codagenix Inc.
United States Attenuated Phase I (48) [389]
First-in-human, randomised, double-blind, placebo-controlled, dose-escalation
Dec 2020 Jun 2021, United Kingdom
Preclinical
CoV2 SAM (LNP)
GSK
United Kingdom RNA Phase I (40) [390]
Open-label, dose escalation, non-randomized
Feb–Jun 2021, United States
Preclinical
COVIGEN [391]
Bionet Asia, Technovalia, University of Sydney
Australia, Thailand DNA Phase I (150) [392]
Double-blind, dose-ranging, randomised, placebo-controlled.
Feb 2021 Jun 2022, Australia, Thailand
Preclinical
MV-014-212 [393]
Meissa Vaccine Inc.
United States Attenuated Phase I (130) [394]
Randomized, double-blinded, multicenter.
Mar 2021 Oct 2022, United States
Preclinical
S-268019
Shionogi
Japan Subunit Phase I–II (300) [395]
Randomized, double-blind, placebo-controlled, parallel-group.
Dec 2020 Jun 2022, Japan
Preclinical
KBP-201
Kentucky Bioprocessing
United States Subunit Phase I–II (180) [396]
First-in-human, observer-blinded, randomized, placebo-controlled, parallel group
Dec 2020 May 2022, United States
Preclinical
AdCLD-CoV19
Cellid Co
South Korea Viral vector Phase I–II (150) [397]
Phase I: Dose Escalation, Single Center, Open.
Phase IIa: Multicenter, Randomized, Open.
Dec 2020 Jul 2021, South Korea
Preclinical
AdimrSC-2f
Adimmune Corporation
Taiwan Subunit (Recombinant RBD +/− Aluminium)Phase I (70) [398]
Randomized, single center, open-label, dose-finding.
Aug–Nov 2020, Taiwan
Preclinical
AKS-452
University Medical Center Groningen
Netherlands Subunit Phase I–II (130) [399]
Non-randomized, Single-center, open-label, combinatorial.
Apr–Jun 2021, Netherlands
Preclinical
GLS-5310
GeneOne Life Science Inc.
South Korea DNA Phase I–II (345) [400]
Multicenter, Randomized, Combined Phase I Dose-escalation and Phase IIa Double-blind.
Dec 2020 Jul 2022, South Korea
Preclinical
Covigenix VAX-001
Entos Pharmaceuticals Inc.
Canada DNA Phase I–II (72) [401]
Placebo-controlled, randomized, observer-blind, dose ranging adaptive.
Mar–Aug 2021, Canada
Preclinical
NBP2001
SK Bioscience Co. Ltd.
South Korea Subunit (Recombinant protein with adjuvanted with alum)Phase I (50) [402]
Placebo-controlled, Randomized, Observer-blinded, Dose-escalation.
Dec 2020 Apr 2021, South Korea
Preclinical
CoVac-1
University of Tübingen
Germany Subunit (Peptide)Phase I–II (104) [403] [404]
Phase I (36): Placebo-controlled, Randomized, Observer-blinded, Dose-escalation.
Phase I/II (68): B-pVAC-SARS-CoV-2: Phase I/II Multicenter Safety and Immunogenicity Trial of Multi-peptide Vaccination to Prevent COVID-19 Infection in Adults With Bcell/ Antibody Deficiency.
Nov 2020 Feb 2022, Germany
Preclinical
bacTRL-Spike
Symvivo
Canada DNA Phase I (24) [405]
Randomized, observer-blind, placebo-controlled.
Nov 2020 Feb 2022, Australia
Preclinical
CORVax12
Providence Health & Services
United States DNA Phase I (36) [406]
Open-label, non-randomized, parallel assignment study to evaluate the safety of prime & boost doses with/without the combination of electroporated IL-12p70 plasmid in 2 age groups: 18-50 years-old and > 50 years-old.
Dec 2020 Jul 2021, United States
Preclinical
ChAdV68-S(SAM-LNP-S)
NIAID, Gritstone Oncology
United States Viral vector Phase I (150) [407]
Open-label, dose and age escalation, parallel design.
Mar 2021 Sep 2022, United States
Preclinical
SpFN COVID-19 vaccine
United States Army Medical Research and Development Command
United States Subunit Phase I (72) [408]
Randomized, double-blind, placebo-controlled.
Apr 2021 Oct 2022, United States
Preclinical
MVA-SARS-2-S(MVA-SARS-2-ST)
University Medical Center Hamburg-Eppendorf
Germany Viral vector Phase I–II (270) [409] [410]
Phase I (30): Open, Single-center.
Phase Ib/IIa (240): Multi-center, Randomized Controlled.
Oct 2020 Mar 2022, Germany
Preclinical
Koçak-19 Inaktif Adjuvanlı COVID-19 vaccine
Kocak Farma
Turkey Inactivated SARS‑CoV‑2 Phase I (38) [411]
Phase 1 Study for the Determination of Safety and Immunogenicity of Different Strengths of Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine, Given Twice Intramuscularly to Healthy Volunteers, in a Placebo Controlled Study Design.
Mar–Jun 2021, Turkey
Preclinical
mRNA-1283
Moderna
United States RNA Phase I (106) [412]
Randomized, observer-blind, dose-ranging study.
Mar 2021 Apr 2022, United States
Preclinical
DS-5670 [413]
Daiichi Sankyo [414]
Japan RNA Phase I–II (152) [415]
A Phase 1/2 Study to Assess the Safety, Immunogenicity and Recommended Dose of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects.
Mar 2021 Jul 2022, Japan
Preclinical
CoV2-OGEN1
Syneos Health, US Specialty Formulations
United States Subunit Phase I (45) [416]
First-In-Human
Jun–Dec 2021, New Zealand
Preclinical
KD-414
KM Biologics Co
Japan Inactivated SARS‑CoV‑2 Phase I–II (210) [417]
Randomized, double blind, placebo control, parallel group. [418]
Mar 2021  Dec 2022, Japan
Preclinical
CoVepiT
OSE Immunotherapeutics
France Subunit Phase I (48) [419] [420]
Randomized, open label.
Apr–Sept 2021, France
Preclinical
HDT-301
Senai Cimatec
Brazil RNA Phase I (90) [421]
Randomized, open-label, dose-escalation.
Aug 2021–Sep 2022, Brazil
Preclinical
SC-Ad6-1
Tetherex Pharmaceuticals
United States Viral vector Phase I (40) [422]
First-In-Human, Open-label, Single Ascending Dose and Multidose.
Jun–Dec 2021, Australia
Preclinical
Unnamed
Osman ERGANIS, Scientific and Technological Research Council of Turkey
Turkey Inactivated SARS‑CoV‑2 Phase I (50) [423]
Phase I Study Evaluating the Safety and Efficacy of the Protective Adjuvanted Inactivated Vaccine Developed Against SARS-CoV-2 in Healthy Participants, Administered as Two Injections Subcutaneously in Two Different Dosages.
Apr–Oct 2021, Turkey
Preclinical
EXG-5003
Elixirgen Therapeutics, Fujita Health University
Japan, United States RNA Phase I–II (60) [424]
First in Human, randomized, placebo-controlled.
Apr 2021 Jan 2023, Japan
Preclinical
mRNACOVID-19 Vaccine
Stemirna Therapeutics Co. Ltd.
China RNA Phase I (240) [425]
Randomized, double-blind, placebo-controlled.
Mar–Jul 2021, China
Preclinical
IVX-411
Icosavax, Seqirus Inc.
United States Virus-like particle Phase I–II (168) [426] [427]
Phase I/II (84): Randomized, observer-blinded, placebo-controlled.
Jun 2021–2022, Australia
Preclinical
QazCoVac-P [428]
Research Institute for Biological Safety Problems
Kazakhstan Subunit Phase I–II (244) [429]
Phase I: Randomized, blind, placebo-controlled.
Phase II: Randomized, open phase.
Jun – Dec 2021, Kazakhstan
Preclinical
LNP-nCOV saRNA-02
MRC/UVRI & LSHTM Uganda Research Unit
Uganda RNA Phase I (42) [430]
A Clinical Trial to Assess the Safety and Immunogenicity of LNP-nCOV saRNA-02, a Self-amplifying Ribonucleic Acid (saRNA) Vaccine, in SARS-CoV-2 Seronegative and Seropositive Uganda Population.
Sep 2021 – Jun 2022, Uganda
Preclinical
Noora [431]
Baqiyatallah University of Medical Sciences
Iran Subunit (RBD protein recombinant vaccine)Phase I (70) [432]
Randomized, double-blinded, placebo-controlled.
Jun–Aug 2021, Iran
Preclinical
Baiya SARS-CoV-2 Vax 1 [433]
Baiya Phytopharm Co Ltd.
ThailandPlant-based Subunit (RBD-Fc + adjuvant)Phase I (96) [434]
Randomized, open-label, dose-finding.
Sep–Dec 2021, Thailand
Preclinical
CVXGA1
CyanVac LLC
United States Viral vector Phase I (80) [435]
Open-label
July–Dec 2021, United States
Preclinical
Unnamed
St. Petersburg Scientific Research Institute of Vaccines and Sera of Russia at the Federal Medical Biological Agency
Russia Subunit (Recombinant)Phase I–II (200) [436]
July–? 2021, Russia
Preclinical
LVRNA009
Liverna Therapeutics Inc.
China RNA Phase I (24) [437]
July–Nov 2021, China
Preclinical
PHH-1V
Hipra [438]
Spain Subunit Phase I–II (30) [439]
Randomized, controlled, observer-blinded, dose-escalation.
Aug–Nov 2021, Spain
Preclinical
ARCT-165
Arcturus Therapeutics
United States RNA Phase I–II (72) [440]
Randomized, observer-blind.
Aug 2021–Mar 2023, Singapore, United States
Preclinical
BCD-250
Biocad
Russia Viral vector Phase I–II (160) [441]
Randomized, double-blind, placebo-controlled, adaptive, seamless phase I/II.
Aug 2021–Aug 2022, Russia
Preclinical
COVID-19-EDV
EnGeneIC
Australia Viral vector Phase I (18) [442]
Open label, non-randomised, dose escalation.
Aug 2021–Jan 2022, Australia
Preclinical
COVIDITY
Scancell
United Kingdom DNA [443] Phase I (40) [444]
Open-label, two-arm.
Sep 2021–Apr 2022, South Africa
Preclinical
SII Bivalent
Novavax
United States Subunit Phase I–II (240) [445]
randomized, observer-blinded, open-label.
Oct–Nov 2021, Australia
Preclinical
EG-COVID
Eyegene
South Korea mRNA Phase I–II (170) [446] [447]
Sep–Dec 2021, South Korea
Preclinical
PIKA COVID-19 vaccine
Yisheng Biopharma
China Subunit Phase I (45) [448]
Open-label, dose-escalation.
Sep–Nov 2021, New Zealand
Preclinical
Unnamed
North's Academy of Medical Science Medical biology institute
North Korea Subunit (spike protein with Angiotensin-converting enzyme 2)Phase I–II (?) [449]
Jul 2020, North Korea
Preclinical
Unnamed
Sinopharm
China Subunit Phase I–II (?) [450]
Apr 2021–?, China
Preclinical
Vabiotech COVID-19 vaccine
Vaccine and Biological Production Company No. 1 (Vabiotech)
Vietnam Subunit Preclinical
Awaited for the conduct on Phase I trial. [451]
?
INO-4802
Inovio
United States DNA Preclinical
Awaited for the conduct on Phase I/II trials. [452]
?
Bangavax (Bancovid) [453] [454]
Globe Biotech Ltd. of Bangladesh
Bangladesh RNA Preclinical
Awaiting for approval from Bangladesh government to conduct the first clinical trial. [455]
?
Unnamed
Indian Immunologicals, Griffith University [456]
Australia, India Attenuated Preclinical?
EPV-CoV-19 [457]
EpiVax
United States Subunit (T cell epitope-based protein)Preclinical?
Unnamed
Intravacc [458]
Netherlands Subunit Preclinical?
CV2CoV [459]
CureVac, GSK
Germany, United Kingdom RNA Preclinical?
DYAI-100 [460] Sorrento Therapeutics, Dyadic International, Inc. [461] United States Subunit Preclinical?
Unnamed [462]
Ministry of Health (Malaysia), Malaysia Institute of Medical Research Malaysia, Universiti Putra Malaysia
Malaysia RNA Preclinical?
CureVac COVID-19 vaccine (CVnCoV)
CureVac, CEPI
Germany RNA (unmodified RNA) [463] Terminated (44,433) [464] [465] [466] [467] [468]
Phase 2b/3 (39,693): Multicenter efficacy and safety trial in adults.
Phase 3 (2,360+180+1,200+1,000=4,740): Randomized, placebo-controlled, multicenter, some observer-blinded, some open-labeled.
Nov 2020 Jun 2022, Argentina, Belgium, Colombia, Dominican Republic, France, Germany, Mexico, Netherlands, Panama, Peru, Spain [469]
Phase I–II (944) [470] [471]
Phase I (284): Partially blind, controlled, dose-escalation to evaluate safety, reactogenicity and immunogenicity.
Phase IIa (660):Partially observer-blind, multicenter, controlled, dose-confirmation.
Jun 2020 Oct 2021, Belgium (phase I), Germany (phase I), Panama (phase IIa), Peru (phase IIa)
Emergency (2)
Sanofi–Translate Bio COVID-19 vaccine (MRT5500) [474]
Sanofi Pasteur and Translate Bio
France, United States RNA Terminated (415) [475]
Interventional, randomized, parallel-group, sequential study consisting of a sentinel cohort followed by the full enrollment cohort. The sentinel cohort is a open-label, step-wise, dose-ranging study to evaluate the safety of 3 dose levels with 2 vaccinations. The full enrollment cohort is a quadruple-blinded study of safety and immunogenicity in 2 age groups, with half receiving a single injection, and the other half receiving 2 injections.
Mar 2021 Sep 2021, Honduras, United States, Australia
Preclinical
AdCOVID
Altimmune Inc.
United States Viral vector Terminated (180) [476] [477]
Double-blind, randomized, placebo-controlled, first-in-Human.
Feb 2021 Feb 2022, United States
Preclinical
LNP-nCoVsaRNA [478]
MRC clinical trials unit at Imperial College London
United Kingdom RNA Terminated (105)
Randomized trial, with dose escalation study (15) and expanded safety study (at least 200)
Jun 2020 Jul 2021, United Kingdom
?
TMV-083
Institut Pasteur
France Viral vector Terminated (90) [479]
Randomized, Placebo-controlled.
Aug 2020 Jun 2021, Belgium, France
?
SARS-CoV-2 Sclamp/ V451 [480] [481] [ unreliable source? ]
UQ, Syneos Health, CEPI, Seqirus
Australia Subunit (molecular clamp stabilized spike protein with MF59)Terminated (120)
Randomised, double-blind, placebo-controlled, dose-ranging.
False positive HIV test found among participants.
Jul–Oct 2020, Brisbane
?
V590 [482] and V591/MV-SARS-CoV-2 [483] Merck & Co. (Themis BIOscience), Institut Pasteur, University of Pittsburgh's Center for Vaccine Research (CVR), CEPI United States, France Vesicular stomatitis virus vector [484] / Measles virus vector [485] [ unreliable source? ]Terminated
In phase I, immune responses were inferior to those seen following natural infection and those reported for other SARS-CoV-2/COVID-19 vaccines. [486]
  1. Latest Phase with published results.
  2. Virus-like particles grown in Nicotiana benthamiana [211]
  3. Phase I–IIa in South Korea in parallel with Phase II–III in the US

Homologous prime-boost vaccination

In July 2021, the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) issued a joint statement reporting that a booster dose is not necessary for those who have been fully vaccinated. [487]

In August 2021, the FDA and the CDC authorized the use of an additional mRNA vaccine dose for immunocompromised individuals. [488] [489] The authorization was extended to cover other specific groups in September 2021. [490] [491] [492]

In October 2021, the FDA and the CDC authorized the use of either homologous or heterologous vaccine booster doses. [493] [494]

Heterologous prime-boost vaccination

In October 2021, the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) authorized the use of either homologous or heterologous vaccine booster doses. [493] [494]

Some experts believe that heterologous prime-boost vaccination courses can boost immunity, and several studies have begun to examine this effect. [495] Despite the absence of clinical data on the efficacy and safety of such heterologous combinations, Canada and several European countries have recommended a heterologous second dose for people who have received the first dose of the Oxford–AstraZeneca vaccine. [496]

In February 2021, the Oxford Vaccine Group launched the Com-COV vaccine trial to investigate heterologous prime-boost courses of different COVID-19 vaccines. [497] As of June 2021, the group is conducting two phase II studies: Com-COV and Com-COV2. [498]

In Com-COV, the two heterologous combinations of the Oxford–AstraZeneca and Pfizer–BioNTech vaccines were compared with the two homologous combinations of the same vaccines, with an interval of 28 or 84 days between doses. [499] [500] [ unreliable medical source? ]

In Com-COV2, the first dose is the Oxford–AstraZeneca vaccine or the Pfizer vaccine, and the second dose is the Moderna vaccine, the Novavax vaccine, or a homologous vaccine equal to the first dose, with an interval of 56 or 84 days between doses. [501]

A study in the UK is evaluating annual heterologous boosters by randomly selecting the following vaccines: Oxford–AstraZeneca, Pfizer–BioNTech, Moderna, Novavax, VLA2001, CureVac, and Janssen. [502]

Heterologous regimes in clinical trial
First doseSecond doseSchedulesCurrent phase (participants), periods and locations
Oxford–AstraZeneca
Pfizer–BioNTech
Oxford–AstraZeneca
Pfizer–BioNTech
Days 0 and 28
Days 0 and 84
Phase II (820) [499]
Feb–Aug 2021, United Kingdom
Sputnik Light Oxford–AstraZeneca
Moderna
BBIBP-CorV
Phase II (121) [503]
Feb–Aug 2021, Argentina
Oxford–AstraZeneca
Pfizer–BioNTech
Oxford–AstraZeneca
Pfizer–BioNTech
Moderna
Novavax
Days 0 and 5684Phase II (1,050) [501]
Mar 2021 Sep 2022, United Kingdom
Convidecia ZF2001 Days 0 and 28
Days 0 and 56
Phase IV (120) [504]
Apr–Dec 2021, China
Oxford–AstraZenecaPfizer–BioNTechDays 0 and 28Phase II (676) [505]
Apr 2021 Apr 2022, Spain
Oxford–AstraZeneca
Pfizer–BioNTech
Moderna
Pfizer–BioNTech
Moderna
Days 0 and 28
Days 0 and 112
Phase II (1,200) [506]
May 2021 Mar 2023, Canada
Pfizer–BioNTech
Moderna
Pfizer–BioNTech
Moderna
Days 0 and 42Phase II (400) [507]
May 2021 Jan 2022, France
Oxford–AstraZenecaPfizer–BioNTechDays 0 and 28
Days 0 and 21–49
Phase II (3,000) [508]
May–Dec 2021, Austria
Janssen Pfizer–BioNTech
Janssen
Moderna
Days 0 and 84Phase II (432) [509]
Jun 2021 Sep 2022, Netherlands

Efficacy

Cumulative incidence curves for symptomatic COVID-19 infections after the first dose of the Pfizer-BioNTech vaccine (tozinameran) or placebo in a double-blind clinical trial. (red: placebo; blue: tozinameran) BNT162b2 vaccine efficacy data.png
Cumulative incidence curves for symptomatic COVID‑19 infections after the first dose of the Pfizer–BioNTech vaccine (tozinameran) or placebo in a double-blind clinical trial. (red: placebo; blue: tozinameran)

Vaccine efficacy is the reduction in risk of getting the disease by vaccinated participants in a controlled trial compared with the risk of getting the disease by unvaccinated participants. [511] An efficacy of 0% means that the vaccine does not work (identical to placebo). An efficacy of 50% means that there are half as many cases of infection as in unvaccinated individuals.[ citation needed ]

COVID-19 vaccine efficacy may be adversely affected if the arm is held improperly or squeezed so the vaccine is injected subcutaneously instead of into the muscle. [512] [513] The CDC guidance is to not repeat doses that are administered subcutaneously. [514]

It is not straightforward to compare the efficacies of the different vaccines because the trials were run with different populations, geographies, and variants of the virus. [515] In the case of COVID‑19 prior to the advent of the delta variant, it was thought that a vaccine efficacy of 67% may be enough to slow the pandemic, but the current vaccines do not confer sterilizing immunity, [516] which is necessary to prevent transmission. Vaccine efficacy reflects disease prevention, a poor indicator of transmissibility of SARS‑CoV‑2 since asymptomatic people can be highly infectious. [517] The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) set a cutoff of 50% as the efficacy required to approve a COVID‑19 vaccine, with the lower limit of the 95% confidence interval being greater than 30%. [518] [519] [520] Aiming for a realistic population vaccination coverage rate of 75%, and depending on the actual basic reproduction number, the necessary effectiveness of a COVID-19 vaccine is expected to need to be at least 70% to prevent an epidemic and at least 80% to extinguish it without further measures, such as social distancing. [521]

The observed substantial efficacy of certain mRNA vaccines even after partial (1-dose) immunization [522] [510] indicates a non-linear dose-efficacy relation already seen in the phase I-II study [523] and suggests that personalization of the vaccine dose (regular dose to the elderly, reduced dose to the healthy young, [524] additional booster dose to the immunosuppressed [525] ) might allow accelerating vaccination campaigns in settings of limited supplies, thereby shortening the pandemic, as predicted by pandemic modeling. [526]

Ranges below are 95% confidence intervals unless indicated otherwise, and all values are for all participants regardless of age, according to the references for each of the trials. By definition, the accuracy of the estimates without an associated confidence interval is unknown publicly. Efficacy against severe COVID-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority. [527] Authorized and approved vaccines have shown the following efficacies:

COVID-19 vaccine efficacy
()
VaccineEfficacy by severity of COVID-19Trial locationRefs
Mild or moderate [upper-alpha 1] Severe without hospitalization or death [upper-alpha 2] Severe with hospitalization or death [upper-alpha 3]
Oxford–AstraZeneca 81% (6091%) [upper-alpha 4] 100% (97.5% CI, 72100%)100% [upper-alpha 5] Multinational [26]
74% (6882%) [upper-alpha 6] 100% [upper-alpha 5] 100% [upper-alpha 5] United States [528]
Pfizer–BioNTech 95% (9098%) [upper-alpha 7] 66% (−125 to 96%) [upper-alpha 8] [upper-alpha 7] Multinational [529]
95% (9098%) [upper-alpha 7] Not reportedNot reportedUnited States [530]
Janssen 66% (5575%) [upper-alpha 9] [upper-alpha 10] 85% (5497%) [upper-alpha 10] 100% [upper-alpha 5] [upper-alpha 10] [upper-alpha 11] Multinational [531]
72% (5882%) [upper-alpha 9] [upper-alpha 10] 86% (−9 to 100%) [upper-alpha 8] [upper-alpha 10] 100% [upper-alpha 5] [upper-alpha 10] [upper-alpha 11] United States
68% (4981%) [upper-alpha 9] [upper-alpha 10] 88% (8100%) [upper-alpha 8] [upper-alpha 10] 100% [upper-alpha 5] [upper-alpha 10] [upper-alpha 11] Brazil
64% (4179%) [upper-alpha 9] [upper-alpha 10] 82% (4695%) [upper-alpha 10] 100% [upper-alpha 5] [upper-alpha 10] [upper-alpha 11] South Africa
Moderna 94% (8997%) [upper-alpha 12] 100% [upper-alpha 5] [upper-alpha 13] 100% [upper-alpha 5] [upper-alpha 13] United States [533]
BBIBP-CorV 78% (6586%)100% [upper-alpha 5] 100% [upper-alpha 5] Multinational [59]
79% (6688%)Not reported79% (2694%) [upper-alpha 8] Multinational [534]
Sputnik V 92% (8695%)100% (94100%)100% [upper-alpha 5] Russia [535]
CoronaVac 51% (3662%) [upper-alpha 14] 84% (5894%) [upper-alpha 14] 100% (56100%) [upper-alpha 14] Brazil [536] [537] [538]
84% (6592%)100% [upper-alpha 5] 100% (20100%) [upper-alpha 8] Turkey [539]
Covaxin 78% (6586%) [upper-alpha 14] 93% (57100%) [upper-alpha 14] India [540] [ unreliable medical source? ]
Sputnik Light 79% [upper-alpha 5] Not reportedNot reportedRussia [541]
Convidecia 66% [upper-alpha 5] [upper-alpha 14] 91% [upper-alpha 5] [upper-alpha 14] Not reportedMultinational [101] [ unreliable medical source? ]
WIBP-CorV 73% (5882%)100% [upper-alpha 5] [upper-alpha 15] 100% [upper-alpha 5] [upper-alpha 15] Multinational [542]
Abdala 92% (8696%)Not reportedNot reportedCuba [543] [544] [ unreliable medical source? ]
Soberana 02 62% [upper-alpha 5] Not reportedNot reportedCuba [545] [ unreliable medical source? ]
Novavax 90% (7595%)100% [upper-alpha 5] [upper-alpha 15] 100% [upper-alpha 5] [upper-alpha 15] United Kingdom [546] [547] [548]
60% (2080%) [upper-alpha 8] 100% [upper-alpha 5] [upper-alpha 15] 100% [upper-alpha 5] [upper-alpha 15] South Africa
90% [upper-alpha 5] Not reportedNot reportedUnited States
Not reportedNot reportedMexico
CureVac 48% [upper-alpha 5] Not reportedNot reportedMultinational [549]
ZyCoV-D 67% [upper-alpha 5] Not reportedNot reportedIndia [550] [ unreliable medical source? ]
ZF2001 82% [upper-alpha 5] Not reportedNot reportedMultinational [551] [ unreliable medical source? ]
SCB-2019 67% [upper-alpha 5] Not reportedNot reportedMultinational [552] [553] [ unreliable medical source? ]
  1. Mild symptoms: fever, dry cough, fatigue, myalgia, arthralgia, sore throat, diarrhea, nausea, vomiting, headache, anosmia, ageusia, nasal congestion, rhinorrhea, conjunctivitis, skin rash, chills, dizziness. Moderate symptoms: mild pneumonia.
  2. Severe symptoms without hospitalization or death for an individual, are any one of the following severe respiratory symptoms measured at rest on any time during the course of observation (on top of having either pneumonia, deep vein thrombosis, dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °C (100 °F)), that however were not persistent/severe enough to cause hospitalization or death: Any respiratory rate ≥30 breaths/minute, heart rate ≥125 beats/minute, oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg.
  3. Severe symptoms causing hospitalization or death, are those requiring treatment at hospitals or results in deaths: dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °C (100 °F), respiratory failure, kidney failure, multiorgan dysfunction, sepsis, shock.
  4. With twelve weeks or more between doses. For an interval of less than six weeks, the trial found an efficacy ≈55% (3370%).
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 A confidence interval was not provided, so it is not possible to know the accuracy of this measurement.
  6. With a four-week interval between doses. Efficacy is "at preventing symptomatic COVID-19".
  7. 1 2 3 COVID-19 symptoms observed in the Pfizer–BioNTech vaccine trials, were only counted as such for vaccinated individuals if they began more than seven days after their second dose, and required presence of a positive RT-PCR test result. Mild/moderate cases required at least one of the following symptoms and a positive test during, or within 4 days before or after, the symptomatic period: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhoea; or vomiting. Severe cases additionally required at least one of the following symptoms: clinical signs at rest indicative of severe systemic illness (RR ≥30 breaths per minute, HR ≥125 beats per minute, SpO2 ≤93% on room air at sea level, or PaO2/FiO2<300mm Hg); respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation, mechanical ventilation, or ECMO); evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors); significant acute renal, hepatic, or neurologic dysfunction; admission to an ICU; death. [529] [530]
  8. 1 2 3 4 5 6 This measurement is not accurate enough to support the high efficacy because the lower limit of the 95% confidence interval is lower than the minimum of 30%.
  9. 1 2 3 4 Moderate cases.
  10. 1 2 3 4 5 6 7 8 9 10 11 12 Efficacy reported 28 days post-vaccination for the Janssen single shot vaccine. A lower efficacy was found for the vaccinated individuals 14 days post-vaccination. [531]
  11. 1 2 3 4 No hospitalizations or deaths were detected 28 days post-vaccination for 19,630 vaccinated individuals in the trials, compared with 16 hospitalizations reported in the placebo group of 19,691 individuals (incidence rate 5.2 per 1000 person-years) [531] and seven COVID-19 related deaths for the same placebo group. [532]
  12. Mild/Moderate COVID-19 symptoms observed in the Moderna vaccine trials, were only counted as such for vaccinated individuals if they began more than 14 days after their second dose, and required presence of a positive RT-PCR test result along with at least two systemic symptoms (fever above 38ºC, chills, myalgia, headache, sore throat, new olfactory and taste disorder) or just one respiratory symptom (cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia). [533]
  13. 1 2 Severe COVID-19 symptoms observed in the Moderna vaccine trials, were defined as symptoms having met the criteria for mild/moderate symptoms plus any of the following observations: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS, (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure <90 mmHg, diastolic BP <60 mmHg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death. No severe cases were detected for vaccinated individuals in the trials, compared with thirty in the placebo group (incidence rate 9.1 per 1000 person-years). [533]
  14. 1 2 3 4 5 6 7 These Phase III data have not been published or peer reviewed.
  15. 1 2 3 4 5 6 No cases detected in trial.

Effectiveness

As of August 2021, data from studies in the U.S. and in other countries found that the COVID-19 vaccines available in the United States are "highly protective against severe illness, hospitalization, and death due to COVID-19". [554] In comparison with fully vaccinated people, the CDC found that unvaccinated people were 5 times more likely to be infected, 10 times more likely to be hospitalized, and 11 times more likely to die. [555] [556]

By late August 2021, after the Delta variant became dominant, studies concluded that COVID-19 vaccines provided 55 percent protection against infection, 80 percent against symptomatic infection, and at least 90 percent against hospitalization. [557] [ medical citation needed ] The Delta variant, which is about 40 percent more contagious than the alpha variant, [558] [ medical citation needed ] became the dominant strain during the spring of 2021. However, the vaccines still protected against severe illness and hospitalizations with slight reduction in effectiveness. [557] [ medical citation needed ] The CDC similarly found that vaccines were 90 percent effective at preventing hospitalizations. [559]

As a result of the CDC reports, President Joe Biden said that "virtually all" COVID-19 hospitalizations and deaths in the U.S. were among unvaccinated people. [560] A study in the state of Washington found that unvaccinated people were six times more likely to test positive for COVID-19, 37 times more likely to be hospitalized, and 67 times more likely to die, compared to those who had been vaccinated. [561]

Researchers note that although current vaccines were not designed against the Delta variant, they nonetheless are highly effective, but to a lesser degree: protection fell from 91% to 66%. [562] [ unreliable source? ][ medical citation needed ] One expert stated that "those who are infected following vaccination are still not getting sick and not dying like was happening before vaccination." [558] "This virus is the most efficient virus for finding new hosts that are vulnerable," stated Dr. Eric Topol, director and founder of the Scripps Research Translational Institute. [558] By late August 2021 the Delta variant accounted for 99 percent of U.S. cases and was found to double the risk of severe illness and hospitalization for those not yet vaccinated. [563]

In September 2021, the European Journal of Epidemiology published a study demonstrating that increases in COVID-19 are unrelated to levels of vaccination across 68 countries and 2947 counties in the United States. The study also indicated that the trend line suggests a marginally positive association such that countries with a higher percentage of their population fully vaccinated have higher COVID-19 cases per 1 million people. The authors of the study advised that sole reliance on vaccination as a primary strategy to mitigate COVID-19 and its adverse consequences needs to be re-examined, especially considering the Delta variant and the likelihood of future variants. [564]

Studies

The real-world studies of vaccine effectiveness measure to which extent a certain vaccine has succeeded in preventing COVID-19 infection, symptoms, hospitalization and death for the vaccinated individuals in a large population under routine conditions that are less than ideal. [565]

  • In Israel, among the 715,425 individuals vaccinated by the Moderna or Pfizer-BioNTech vaccines during the period 20 December 2020, to 28 January 2021, it was observed for the period starting seven days after the second shot, that only 317 people (0.04%) became sick with mild/moderate COVID-19 symptoms and only 16 people (0.002%) were hospitalized. [566]
  • The Pfizer-BioNTech and Moderna COVID-19 vaccines provide highly effective protection, according to a report from the U.S. Centers for Disease Control and Prevention (CDC). Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%. [567]
  • 15,121 health care workers from 104 hospitals in England, that all had tested negative for COVID-19 antibodies prior of the study, were followed by RT-PCR tests twice a week from 7 December 2020 to 5 February 2021, during a time when the Alpha variant (lineage B.1.1.7) was in circulation as the dominant variant. The study compared the positive results for the 90.7% vaccinated share of their cohort with the 9.3% unvaccinated share, and found that the Pfizer-BioNTech vaccine reduced all infections (including asymptomatic), by 72% (58–86%) three weeks after the first dose and 86% (76–97%) one week after the second dose. [568] [ needs update ]
  • A study of the general population in Israel conducted from 17 January to 6 March 2021, during a time when the Alpha variant was in circulation as the dominant variant, found that the Pfizer vaccine reduced asymptomatic COVID-19 infections by 94% and symptomatic COVID-19 infections by 97%. [569]
  • A study, among pre-surgical patients across the Mayo Clinic system in the United States, showed that mRNA vaccines were 80% protective against asymptomatic infections. [570]
  • A study in England found that a single dose of the Oxford–AstraZeneca COVID-19 vaccine is about 73% (2790%) effective in people aged 70 and older. [571]
()
VaccineEffectiveness by severity of COVID-19Study locationRefs
AsymptomaticSymptomaticHospitalizationDeath
Oxford–AstraZeneca 70% (6971%)Not reported87% (8588%)90% (8892%)Brazil [572] [ unreliable medical source? ]
Not reported89% (7894%) [lower-roman 1] Not reportedEngland [574]
Not reported89% [lower-roman 2] Argentina [575]
Pfizer–BioNTech 92% (9192%)97% (9797%)98% (9798%)97% (9697%)Israel [576]
92% (8895%)94% (8798%)87% (55100%)97% [lower-roman 2] Israel [577] [569]
Not reported78% (7779%)98% (9699%)96% (9597%)Uruguay [578]
85% (7496%)Not reportedEngland [579]
90% (6897%)Not reported100% [lower-roman 2] [lower-roman 3] United States [567]
Moderna 90% (6897%)Not reported100% [lower-roman 2] [lower-roman 3] United States [567]
BBIBP-CorV Not reported84% [lower-roman 2] Argentina [575]
50% (4952%)Not reported94% (9196%)Peru [580]
Sputnik V Not reported98% [lower-roman 2] Not reportedRussia [581] [582]
Not reported98% [lower-roman 2] 100% [lower-roman 2] [lower-roman 3] 100% [lower-roman 2] [lower-roman 3] United Arab Emirates [583]
Not reported93% [lower-roman 2] Argentina [575]
CoronaVac 54% (5355%)Not reported73% (7274%)74% (7375%)Brazil [572]
Not reported66% (6567%)88% (8788%)86% (8588%)Chile [584] [585]
Not reported60% (5961%)91% (8993%)95% (9396%)Uruguay [578]
Not reported94% [lower-roman 2] 96% [lower-roman 2] 98% [lower-roman 2] Indonesia [586] [587]
Not reported80% [lower-roman 2] 86% [lower-roman 2] 95% [lower-roman 2] Brazil [588] [589]
Sputnik Light 79% (7582%) [lower-roman 2] [lower-roman 4] Not reported88% (8092%) [lower-roman 2] [lower-roman 4] 85% (7591%) [lower-roman 2] [lower-roman 4] Argentina [590]
  1. Data collected while the Alpha variant was already dominant. [573]
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 A confidence interval was not provided, so it is not possible to know the accuracy of this measurement.
  3. 1 2 3 4 No cases detected in study.
  4. 1 2 3 Participants aged 60 to 79.

Critical coverage

While the most immediate goal of vaccination during a pandemic is to protect individuals from severe disease, a long-term goal is to eventually eradicate it. To do so, the proportion of the population that must be immunized must be greater than the critical vaccination coverage . This value can be calculated from the basic reproduction number and the vaccine effectiveness against transmission as: [591]

Assuming R0 ≈ 2.87 for SARS-CoV-2, [592] then, for example, the coverage level would have to be greater than 72.4% for a vaccine that is 90% effective against transmission. Using the same relationship, the required effectiveness against transmission can be calculated as:

Assuming the same R0 ≈ 2.87, the effectiveness against transmission would have to be greater than 86.9% for a realistic coverage level of 75% [521] or 65.2% for an impossible coverage level of 100%. Less effective vaccines would not be able to eradicate the disease.

Several post-marketing studies have already estimated the effectiveness of some vaccines against asymptomatic infection. Prevention of infection has an impact on slowing transmission (particularly asymptomatic and pre-symptomatic), but the exact extent of this effect is still under investigation. [593]

Some variants of SARS-CoV-2 are more transmissible, showing an increased effective reproduction number, indicating an increased basic reproduction number. Controlling them requires greater vaccine coverage, greater vaccine effectiveness against transmission, or a combination of both.

In July 2021, several experts expressed concern that achieving herd immunity may not currently be possible because the Delta variant is transmitted among those immunized with current vaccines. [594] The CDC published data showing that vaccinated people could transmit the Delta strain, something officials believed was not possible with other variants. [595]

Variants

World Health Organization video describing how variants proliferate in unvaccinated areas.

The interplay between the SARS-CoV-2 virus and its human hosts was initially natural but is now being altered by the prompt availability of vaccines. [596] The potential emergence of a SARS-CoV-2 variant that is moderately or fully resistant to the antibody response elicited by the COVID-19 vaccines may necessitate modification of the vaccines. [597] The emergence of vaccine-resistant variants is more likely in a highly vaccinated population with uncontrolled transmission. [598] Trials indicate many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19. [599] As of February 2021, the US Food and Drug Administration believed that all FDA authorized vaccines remained effective in protecting against circulating strains of SARS-CoV-2. [597]

Alpha (lineage B.1.1.7)

Limited evidence from various preliminary studies reviewed by the WHO indicated retained efficacy/effectiveness against disease from Alpha with the Oxford–AstraZeneca vaccine, Pfizer–BioNTech and Novavax, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated retained antibody neutralization against Alpha with most of the widely distributed vaccines (Sputnik V, Pfizer–BioNTech, Moderna, CoronaVac, BBIBP-CorV, Covaxin), minimal to moderate reduction with the Oxford–AstraZeneca and no data for other vaccines yet. [600]

In December 2020, a new SARS‑CoV‑2 variant, the Alpha variant or lineage B.1.1.7, was identified in the UK. [601]

Early results suggest protection to the variant from the Pfizer-BioNTech and Moderna vaccines. [602] [603]

One study indicated that the Oxford–AstraZeneca COVID-19 vaccine had an efficacy of 42–89% against Alpha, versus 71–91% against other variants. [604] [ unreliable medical source? ]

Preliminary data from a clinical trial indicates that the Novavax vaccine is ~96% effective for symptoms against the original variant and ~86% against Alpha. [605]

Beta (lineage B.1.351)

Limited evidence from various preliminary studies reviewed by the WHO have indicated reduced efficacy/effectiveness against disease from Beta with the Oxford–AstraZeneca vaccine (possibly substantial), Novavax (moderate), Pfizer–BioNTech and Janssen (minimal), with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated possibly reduced antibody neutralization against Beta with most of the widely distributed vaccines (Oxford–AstraZeneca, Sputnik V, Janssen, Pfizer–BioNTech, Moderna, Novavax; minimal to substantial reduction) except CoronaVac and BBIBP-CorV (minimal to modest reduction), with no data for other vaccines yet. [600]

Moderna has launched a trial of a vaccine to tackle the Beta variant or lineage B.1.351. [606] On 17 February 2021, Pfizer announced neutralization activity was reduced by two-thirds for this variant, while stating that no claims about the efficacy of the vaccine in preventing illness for this variant could yet be made. [607] Decreased neutralizing activity of sera from patients vaccinated with the Moderna and Pfizer-BioNTech vaccines against Beta was later confirmed by several studies. [603] [608] On 1 April 2021, an update on a Pfizer/BioNTech South African vaccine trial stated that the vaccine was 100% effective so far (i.e., vaccinated participants saw no cases), with six of nine infections in the placebo control group being the Beta variant. [609]

In January 2021, Johnson & Johnson, which held trials for its Janssen vaccine in South Africa, reported the level of protection against moderate to severe COVID-19 infection was 72% in the United States and 57% in South Africa. [54]

On 6 February 2021, the Financial Times reported that provisional trial data from a study undertaken by South Africa's University of the Witwatersrand in conjunction with Oxford University demonstrated reduced efficacy of the Oxford–AstraZeneca COVID-19 vaccine against the variant. [610] The study found that in a sample size of 2,000 the AZD1222 vaccine afforded only "minimal protection" in all but the most severe cases of COVID-19. [611] On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of about a million doses of the vaccine whilst they examine the data and await advice on how to proceed. [611] [612]

In March 2021, it was reported that the "preliminary efficacy" of the Novavax vaccine (NVX-CoV2373) against Beta for mild, moderate, or severe COVID-19 [613] for HIV-negative participants is 51%.[ medical citation needed ]

Gamma (lineage P.1)

Limited evidence from various preliminary studies reviewed by the WHO have indicated likely retained efficacy/effectiveness against disease from Gamma with CoronaVac and BBIBP-CorV, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated retained antibody neutralization against Gamma with Oxford–AstraZeneca and CoronaVac (no to minimal reduction) and slightly reduced neutralization with Pfizer–BioNTech and Moderna (minimal to moderate reduction), with no data for other vaccines yet. [600]

The Gamma variant or lineage P.1 variant (also known as 20J/501Y.V3), initially identified in Brazil, seems to partially escape vaccination with the Pfizer-BioNTech vaccine. [608]

Delta (lineage B.1.617.2)

Limited evidence from various preliminary studies reviewed by the WHO have indicated likely retained efficacy/effectiveness against disease from Delta with the Oxford–AstraZeneca vaccine and Pfizer–BioNTech, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated reduced antibody neutralization against Delta with single-dose Oxford–AstraZeneca (substantial reduction), Pfizer–BioNTech and Covaxin (modest to moderate reduction), with no data for other vaccines yet. [600]

In October 2020, a new variant was discovered in India, which was named lineage B.1.617. There were very few detections until January 2021, but by April it had spread to at least 20 countries in all continents except Antarctica and South America. [614] [615] [616] Mutations present in the spike protein in the B.1.617 lineage are associated with reduced antibody neutralization in laboratory experiments. [617] [618] The variant has frequently been referred to as a 'Double mutant', even though in this respect it is not unusual. [619] the latter two of which may cause it to easily avoid antibodies. [620] In an update on 15 April 2021, PHE designated lineage B.1.617 as a 'Variant under investigation', VUI-21APR-01. [621] On 6 May 2021, Public Health England escalated lineage B.1.617.2 from a Variant Under Investigation to a Variant of Concern based on an assessment of transmissibility being at least equivalent to the Alpha variant. [622]

Effect of neutralizing antibodies

One study found that the in vitro concentration (titer) of neutralizing antibodies elicited by a COVID-19 vaccine is a strong correlate of immune protection. The relationship between protection and neutralizing activity is nonlinear. A neutralization as low as 3% (95% CI, 113%) of the level of convalescence results in 50% efficacy against severe disease, with 20% (1428%) resulting in 50% efficacy against detectable infection. Protection against infection quickly decays, leaving individuals susceptible to mild infections, while protection against severe disease is largely retained and much more durable. The observed half-life of neutralizing titers was 65 days for mRNA vaccines (Pfizer–BioNTech, Moderna) during the first 4 months, increasing to 108 days over 8 months. Greater initial efficacy against infection likely results in a higher level of protection against serious disease in the long term (beyond 10 years, as seen in other vaccines such as smallpox, measles, mumps, and rubella), although the authors acknowledge that their simulations only consider protection from neutralizing antibodies and ignore other immune protection mechanisms, such as cell-mediated immunity, which may be more durable. This observation also applies to efficacy against variants and is particularly significant for vaccines with a lower initial efficacy; for example, a 5-fold reduction in neutralization would indicate a reduction in initial efficacy from 95% to 77% against a specific variant, and from a lower efficacy of 70% to 32% against that variant. For the Oxford–AstraZeneca vaccine, the observed efficacy is below the predicted 95% confidence interval. It is higher for Sputnik V and the convalescent response, and is within the predicted interval for the other vaccines evaluated (Pfizer–BioNTech, Moderna, Janssen, CoronaVac, Covaxin, Novavax). [623]

Side effects

Serious adverse events associated with receipt of new vaccines targeting COVID-19 are of high interest to the public. [624] All vaccines that are administered via intramuscular injection, including COVID-19 vaccines, have side effects related to the mild trauma associated with the procedure and introduction of a foreign substance into the body. [625] These include soreness, redness, rash, and inflammation at the injection site. Other common side effects include fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain) which generally resolve within a few days. [626] One less-frequent side effect (that generally occurs in less than 1 in 1,000 people) is hypersensitivity (allergy) to one or more of the vaccine's ingredients, which in some rare cases may cause anaphylaxis. [627] [628] [629] [630] More serious side effects are very rare because a vaccine would not be approved even for emergency use if it had any known frequent serious adverse effects.[ citation needed ]

Reporting

Most countries operate some form of adverse effects reporting scheme, for example Vaccine Adverse Event Reporting System in the United States and the Yellow Card Scheme [631] in the United Kingdom. In some of these, the data is open to public scrutiny, for example, in the UK, a weekly summary report is published. [632] Concerns have been raised regarding both over- [633] and under-reporting[ citation needed ] of adverse effects.

UK

In the UK, as of 22 September 2021, following the administering of over 48 million first vaccine doses and over 44 million second vaccine doses, there had been 347,447 suspected Covid-19 vaccine related events ('suspected adverse reactions', or 'ADRs') recorded in the Yellow Card system. The majority of these were reports of relatively minor effects (local reactions or temporary flu-like symptoms). Among more serious ADRs, the largest case load came from suspected thrombo-embolic events, of which a total of 439 were recorded, 74 of these fatal. [632] A total of 1,682 suspected fatal ADRs were recorded. [632] For comparison, at this date, the UK had had over 7,500,000 confirmed cases of Covid-19 and over 136,000 people had died within 28 days of a positive test for coronavirus. [632]

Embolic and thrombotic events

The Janssen COVID-19 vaccine reported rare formation of blood clots in the blood vessels in combination with low levels of blood platelets known as thrombosis with thrombocytopenia syndrome (TTS) which occurred at a rate of about 7 per 1 million vaccinated women ages 18–49 years old; and even more rarely for other populations. [634] According to the CDC, very rare cases of myocarditis and pericarditis have been reported in the United States, in about 13 per million young people (mostly in males and mostly over the age of 16), after vaccination with the Pfizer–BioNTech's or Moderna's vaccines. [635] According to reports, the recovery from these rare side effects is quick in most individuals, following adequate treatment and rest. [636]

Hematologic malignancies

In a study on the serologic response to COVID-19 messenger RNA vaccines among patients with lymphoma, leukemia and myeloma, it was found that one-quarter of patients did not produce measurable antibodies, varying by blood cancer type. Patients with these conditions need to take precautions to avoid exposure to COVID-19. [637]

Related Research Articles

COVID-19 vaccine Vaccine designed to provide acquired immunity against SARS-CoV-2

A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19. The COVID‑19 vaccines are widely credited for their role in reducing the spread, severity, and death caused by COVID-19.

Moderna COVID-19 vaccine RNA COVID-19 vaccine

The Moderna COVID‑19 vaccine, codenamed mRNA-1273 and sold under the brand name Spikevax, is a COVID-19 vaccine developed by American company Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA). It is authorized for use in people aged twelve years and older in some jurisdictions and for people eighteen years and older in other jurisdictions to provide protection against COVID-19 which is caused by infection by the SARS-CoV-2 virus. It is designed to be administered as two or three 0.5 mL doses given by intramuscular injection at an interval of at least 28 days apart.

Convidecia Vaccine against COVID-19

AD5-nCOV, trade-named Convidecia, is a single-dose viral vector vaccine for COVID-19 developed by CanSino Biologics. It conducted its Phase III trials in Argentina, Chile, Mexico, Pakistan, Russia, and Saudi Arabia with 40,000 participants.

CoronaVac Vaccine against COVID-19

CoronaVac, also known as the Sinovac COVID-19 vaccine, is an inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. It was Phase III clinical trialled in Brazil, Chile, Indonesia, the Philippines, and Turkey and relies on traditional technology similar to BBIBP-CorV and Covaxin, other inactivated-virus COVID-19 vaccines. CoronaVac does not need to be frozen and both the final product and the raw material for formulating CoronaVac can be transported refrigerated at 2–8 °C (36–46 °F), temperatures at which flu vaccines are kept.

Valneva COVID-19 vaccine Vaccine candidate against COVID-19

Valneva COVID-19 vaccine, also known as the VLA2001 and VLA2101 , is a COVID-19 vaccine candidate developed by French biotechnology company Valneva SE in collaboration with American company Dynavax Technologies.

ZF2001 Vaccine against COVID-19

ZF2001, trade-named ZIFIVAX or ZF-UZ-VAC-2001, is an adjuvanted protein subunit COVID-19 vaccine developed by Anhui Zhifei Longcom in collaboration with the Institute of Microbiology at the Chinese Academy of Sciences. The vaccine candidate is in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan.

EpiVacCorona EpiVacCorona vaccine against COVID-19

EpiVacCorona is a peptide-based vaccine against COVID-19 developed by the VECTOR center of Virology. It consists of three chemically synthesized peptides that are conjugated to a large carrier protein. This protein is a fusion product of a viral nucleocapsid protein and a bacterial MBP protein. The third phase of a clinical trial, which should show whether the vaccine is able to protect people from COVID-19 or not, was launched in November 2020 with more than three thousand participants.

CureVac COVID-19 vaccine Vaccine candidate against COVID-19

The CureVac COVID-19 vaccine was a COVID-19 vaccine candidate developed by CureVac N.V. and the Coalition for Epidemic Preparedness Innovations (CEPI). The vaccine showed inadequate results in its Phase III trials with only 47% efficacy.

SCB-2019 Vaccine candidate against COVID-19

SCB-2019 is a protein subunit COVID-19 vaccine developed by Clover Biopharmaceuticals using an adjuvant from Dynavax technologies. Positive results of Phase I trials for the vaccine were published in The Lancet and the vaccine completed enrollment of 29,000 participants in Phase II/III trials in July 2021. In September 2021, SCB-2019 announced Phase III results showing 67% efficacy against all cases of COVID-19 and 79% efficacy against all cases of the Delta variant. Additionally, the vaccine was 84% effective against moderate cases and 100% effective against hospitalization.

QazCovid-in Vaccine candidate against COVID-19

QazCovid-in, commercially known as QazVac, is a COVID-19 vaccine developed by the Research Institute for Biological Safety Problems in Kazakhstan. QazCoVac-P is a second COVID-19 vaccine developed by the Kazakh Biosafety Research Institute and in clinical trials.

Nanocovax Vaccine candidate against COVID-19

Nanocovax is a Vietnamese COVID-19 vaccine candidate developed by Nanogen Pharmaceutical Biotechnology JSC. It is a subunit vaccine.

Sinopharm WIBP COVID-19 vaccine Vaccine against COVID-19

The Sinopharm WIBP COVID-19 vaccine, also known as WIBP-CorV, is one of two inactivated virus COVID-19 vaccines developed by Sinopharm. Peer-reviewed results show WIBP-CorV 72.8% effective against symptomatic cases and 100% against severe cases. The other inactivated virus COVID-19 vaccine developed by Sinopharm is BBIBP-CorV which is comparably more successful. 1 billion doses are expected to be produced per year.

UB-612 Vaccine candidate against COVID-19

UB-612 is a COVID-19 vaccine candidate developed by United Biomedical, Inc. Asia, Vaxxinity, and DASA. It is a peptide vaccine.

Viral vector vaccine Type of vaccine

A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material coding for a desired antigen into the recipient's host cells. As of April 2021, six viral vector vaccines have been authorized for use in human at least one country: four COVID-19 vaccines and two Ebola vaccines.

NDV-HXP-S Vaccine candidate against COVID-19

NDV-HXP-S is a COVID-19 vaccine candidate developed by a team led by Jason McLellan at the University of Texas at Austin, together with groups from the Icahn School of Medicine at Mount Sinai and the National Institute of Allergy and Infectious Diseases Vaccine Research Center, based on an improved spike protein central to its resilience and efficacy.

Sputnik Light Vaccine against COVID-19

Sputnik Light is a single dose COVID-19 vaccine developed by the Gamaleya Research Institute of Epidemiology and Microbiology. It consists of the first dose of the Sputnik V vaccine, which is based on the Ad26 vector, and it can be stored at a normal refrigerator temperature of 2–8 °C (36–46 °F). The institute says this version would be ideally suited for areas with acute outbreaks, allowing more people to be vaccinated quickly. It will also be used as a third (booster) dose for those who received Sputnik V at least 6 months earlier.

COVI-VAC (U.S. COVID-19 vaccine) Vaccine candidate against COVID-19

COVI-VAC is a COVID-19 vaccine being developed by Codagenix, Inc. It is currently in Phase I clinical trials, involving 48 participants which runs from December 2020 to June 2021.

COVID-19 vaccination in Thailand

COVID-19 vaccination in Thailand is an ongoing mass immunization in response to the ongoing pandemic in the country.

COVAX-19 Vaccine candidate against COVID-19

COVAX-19 is a recombinant protein-based COVID-19 vaccine developed by South Australian based biotech company Vaxine. It is under clinical trial in collaboration with the Iranian company CinnaGen.

ARCT-154 Vaccine candidate against COVID-19

ARCT-154, also known as VBC-COV19-154 in Vietnam, is a COVID-19 vaccine candidate developed by Arcturus Therapeutics. For its development, Arcturus collaborated with Vinbiocare, a Vietnamese company, for support with clinical trials and manufacturing.

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