ChAdOx1

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ChAdOx1 is an adenoviral vector for vaccines that was developed by the Jenner Institute, University of Oxford. The vector is a chimpanzee adenovirus modified to avoid its replication. [1]

Contents

Adenoviruses are effective vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same disadvantages. Therefore, investigators have tested new vaccines using the chimp adenovirus ChAdOx1 as a vector. For example, a vaccine for influenza infection was designed using the vector expressing influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1), creating a vaccine candidate named ChAdOx1 NP+M1. [1]

Virology

ChAdOx1 has been derived from a chimpanzee adenovirus (ChAd) serotype Y25 engineered by λ red recombination to exchange the native E4 orf4, orf6 and orf6/7 genes for those from human adenovirus HAdV-C5. [2] [3] Serotype Y25 belongs to the species Human mastadenovirus E of genus Mastadenovirus .[ citation needed ]

Clinical trials

It has been demonstrated that the adenoviridae vector ChAdOx1 can be used to make vaccinations that are protective against Middle East Respiratory Syndrome (MERS) in mice and able to induce immune response against MERS in humans. [4] [5]

The vector was also used to create a vaccine against Nipah which was effective in hamsters (but never proven in humans), [6] in addition to a potential vaccine for Rift Valley Fever that was protective in sheep, goats, and cattle (but not proven in humans). [7]

The adenovirus expressing the antigen 85A (ChAdOx1 85A), is used as vector for a tuberculosis vaccine candidate. [8]

In 2017, the ChAdOx1 vector was used in a trial for a vaccine candidate against human malaria infection. The researchers studied two candidate vaccines ChAdOx1 LS2 along with MVA LS2. The former, encoding a malaria liver-stage dual antigen LS2 (LSA1 and LSAP2) fused with the transmembrane domain from shark invariant chain. And the latter, a Modified Vaccinia Ankara (MVA) vector encoding the LS2 fused to the C-terminal end of the leader sequence of tPA. The trial reached the phase I/IIa. [9]

There are also investigation lines that use the vector for vaccines against the Zika virus (ChAdOx1 ZIKV) [10] and the Chikungunya virus (ChAdOx1 sCHIKV). [11]

The ChAdOx1 vector has been used as a platform for a vaccine against coronavirus disease since the beginning of the COVID-19 pandemic. [12] [13] [14] [15] Sarah Gilbert leads the work on this vaccine candidate alongside Andrew Pollard, Teresa Lambe, Sandy Douglas, Catherine Green and Adrian Hill. [16] The COVID-19 vaccine, known now as ChAdOx1 nCoV-19 or AZD1222, makes use of this vector, which stimulates an immune response against the coronavirus spike protein. [12] [13] Animal studies began in March 2020, and recruitment of 510 human participants for a phase I/II trial began on 27 March, [17] [18] [19] and the results were presented in October. [20] On 30 December 2020, the vaccine was approved for use [21] in the UK's vaccination programme.

Related Research Articles

<i>Adenoviridae</i> Family of viruses

Adenoviruses are medium-sized, nonenveloped viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.

Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine against smallpox and mpox, having fewer side effects than smallpox vaccines derived from other poxviruses.

<span class="mw-page-title-main">Viral vector</span> Biotechnology to deliver genetic material into a cell

Viral vectors are modified viruses designed to deliver genetic material into cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, agriculture, and medicine.

<span class="mw-page-title-main">Adenovirus vaccine</span>

An adenovirus vaccine is a vaccine against adenovirus infection. According to American CDC, "There is currently no adenovirus vaccine available to the general public.

A homologous booster shot involves the administration of the same vaccine as previously administered, while a heterologous booster shot involves the administration of a different vaccine.

"Heterologous prime-boost immunization is administration of two different vectors or delivery systems expressing the same or overlapping antigenic inserts."

"An effective vaccine usually requires more than one time immunization in the form of prime-boost. Traditionally the same vaccines are given multiple times as homologous boosts. New findings suggested that prime-boost can be done with different types of vaccines containing the same antigens. In many cases such heterologous prime-boost can be more immunogenic than homologous prime-boost."

Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus.

<span class="mw-page-title-main">Ebola vaccine</span> Vaccine against Ebola

Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had been used extensively in the Kivu Ebola epidemic under a compassionate use protocol. During the early 21st century, several vaccine candidates displayed efficacy to protect nonhuman primates against lethal infection.

Sir Adrian Vivian Sinton Hill, is a British-Irish vaccinologist who is Director of the Jenner Institute and Lakshmi Mittal and Family Professor of Vaccinology at the University of Oxford, an honorary Consultant Physician in Infectious Diseases, and Fellow of Magdalen College, Oxford. Hill is a leader in the field of malaria vaccine development and was a co-leader of the research team which produced the Oxford–AstraZeneca COVID-19 vaccine, along with Professor Sarah Gilbert of the Jenner Institute and Professor Andrew Pollard of the Oxford Vaccine Group.

A Zika virus vaccine is designed to prevent the symptoms and complications of Zika virus infection in humans. As Zika virus infection of pregnant women may result in congenital defects in the newborn, the vaccine will attempt to protect against congenital Zika syndrome during the current or any future outbreak. As of April 2019, no vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials. The goal of a Zika virus vaccine is to produce specific antibodies against the Zika virus to prevent infection and severe disease. The challenges in developing a safe and effective vaccine include limiting side effects such as Guillain-Barré syndrome, a potential consequence of Zika virus infection. Additionally, as dengue virus is closely related to Zika virus, the vaccine needs to minimize the possibility of antibody-dependent enhancement of dengue virus infection.

<span class="mw-page-title-main">Sarah Gilbert</span> English vaccinologist (born 1962)

Dame Sarah Catherine Gilbert FRS is an English vaccinologist who is a Professor of Vaccinology at the University of Oxford and co-founder of Vaccitech. She specialises in the development of vaccines against influenza and emerging viral pathogens. She led the development and testing of the universal flu vaccine, which underwent clinical trials in 2011.

<span class="mw-page-title-main">COVID-19 vaccine</span> Vaccine 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).

<span class="mw-page-title-main">Barinthus Biotherapeutics</span> Biotechnology company in Oxford, England

Barinthus Biotherapeutics plc is a biotechnology company developing immunotherapies for infectious diseases, cancer and autoimmune diseases such as hepatitis B, HPV and prostate cancer. Formerly known as Vaccitech plc, in November 2023 the company announced that it had renamed itself to Barinthus Biotherapeutics plc. As of 2024, the company employs more than 100 people.

<span class="mw-page-title-main">Oxford–AstraZeneca COVID-19 vaccine</span> Viral vector vaccine for prevention of COVID-19 by Oxford University and AstraZeneca

The Oxford–AstraZeneca COVID‑19 vaccine, sold under the brand names Covishield and Vaxzevria among others, is a viral vector vaccine for the prevention of COVID-19. It was developed in the United Kingdom by Oxford University and British-Swedish company AstraZeneca, using as a vector the modified chimpanzee adenovirus ChAdOx1. The vaccine is given by intramuscular injection. Studies carried out in 2020 showed that the efficacy of the vaccine is 76.0% at preventing symptomatic COVID-19 beginning at 22 days following the first dose and 81.3% after the second dose. A study in Scotland found that, for symptomatic COVID-19 infection after the second dose, the vaccine is 81% effective against the Alpha variant and 61% against the Delta variant.

<span class="mw-page-title-main">Sputnik V COVID-19 vaccine</span> Russian vaccine against COVID-19

Sputnik V or Gam-COVID-Vac is an adenovirus viral vector vaccine for COVID-19 developed by the Gamaleya Research Institute of Epidemiology and Microbiology in Russia. It is the world's first registered combination vector vaccine for the prevention of COVID-19, having been registered on 11 August 2020 by the Russian Ministry of Health.

GamEvac-Combi is a heterologous VSV- and Ad5-vectored Ebola vaccine. There is also a version called GamEvac which is a homologous Ad5-vectored vaccine. GamEvac-Combi was developed by Gamaleya Research Institute of Epidemiology and Microbiology. As of 2015 the vaccine has been licensed in Russia for emergency use, on the basis of Phase 1 and Phase 2 clinical trials.

<span class="mw-page-title-main">GRAd-COV2</span> Vaccine candidate against COVID-19

GRAd-COV2 is a COVID-19 vaccine candidate developed by ReiThera Srl and Lazzaro Spallanzani National Institute for Infectious Diseases. It is based on a novel replication defective Gorilla Adenovirus and encodes for SARS-COV-2 full length prefusion stabilized Spike protein. More specifically, the vector used is the simian group C adenovirus GRAd32, isolated from a captive gorilla, with a genome deleted of the entire E1 and E3 regions and the native E4 region replaced with the E4 orf6 of human adenovirus 5 (hAd5).

<span class="mw-page-title-main">Viral vector vaccine</span> Type of vaccine

A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.

<span class="mw-page-title-main">COVID-19 vaccine clinical research</span> Clinical research to establish the characteristics of COVID-19 vaccines

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<span class="mw-page-title-main">Riccardo Cortese</span> Italian scientist and entrepreneur

Riccardo Cortese was an Italian scientist, entrepreneur, and innovator in the field of gene expression, drug discovery and genetic vaccines. His work led to the development of novel therapeutic strategies for the prevention and cure of viral infections, including HIV, HCV, Ebola and RSV. He pioneered a novel platform technology based on simian adenoviral vectors for prophylactic and therapeutic vaccines, and authored more than 300 publications in peer-reviewed journals in the field of gene expression, transcriptional control, molecular virology and immunology.

Christine Rollier is a French immunologist who is a professor at the University of Surrey. She focusses on the development of vaccines to treat infectious diseases. In particular, Rollier has focussed on the development of vaccinations to eliminate the plague.

References

  1. 1 2 Antrobus RD, Coughlan L, Berthoud TK, Dicks MD, Hill AV, Lambe T, Gilbert SC (March 2014). "Clinical assessment of a novel recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved Influenza A antigens". Molecular Therapy. 22 (3): 668–674. doi: 10.1038/mt.2013.284 . PMC   3944330 . PMID   24374965.
  2. ↑ Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC, et al. (13 July 2012). "A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity". PLOS ONE. 7 (7): e40385. Bibcode:2012PLoSO...740385D. doi: 10.1371/journal.pone.0040385 . PMC   3396660 . PMID   22808149.
  3. ↑ Morris SJ, Sebastian S, Spencer AJ, Gilbert SC (September 2016). "Simian adenoviruses as vaccine vectors". Future Virology. 11 (9): 649–659. doi:10.2217/fvl-2016-0070. PMC   5842362 . PMID   29527232.
  4. ↑ Munster VJ, Wells D, Lambe T, Wright D, Fischer RJ, Bushmaker T, et al. (December 2017). "Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model". npj Vaccines. 2 (1): 28. doi:10.1038/s41541-017-0029-1. PMC   5643297 . PMID   29263883.
  5. ↑ "New MERS Coronavirus vaccine clinical trial starts in Saudi Arabia". 20 December 2019. Archived from the original on 27 March 2020. Retrieved 5 December 2020.
  6. ↑ van Doremalen N, Lambe T, Sebastian S, Bushmaker T, Fischer R, Feldmann F, et al. (June 2019). "A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters". PLOS Neglected Tropical Diseases. 13 (6): e0007462. doi: 10.1371/journal.pntd.0007462 . PMC   6581282 . PMID   31170144.
  7. ↑ Warimwe GM, Gesharisha J, Carr BV, Otieno S, Otingah K, Wright D, et al. (February 2016). "Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever". Scientific Reports. 6 (1): 20617. Bibcode:2016NatSR...620617W. doi:10.1038/srep20617. PMC   4742904 . PMID   26847478.
  8. ↑ "Helen McShane". Nuffield Department of Medicine. Archived from the original on 26 August 2020. Retrieved 5 December 2020.
  9. ↑ Clinical trial number NCT03203421 for "A Safety and Efficacy Study of ChAdOx1 LS2 and MVA LS2" at ClinicalTrials.gov
  10. ↑ López-Camacho C, Dowall S, Graham V, Findlay-Wilson S, Rayner E, Kim YC, et al. (14 January 2019). "A Zika vaccine based on chimpanzee adenovirus ChAdOx1 elicits lineage-transcending sterile immunity and prevents colonisation of brain and ovaries". bioRxiv   10.1101/514877 .
  11. ↑ López-Camacho C, Kim YC, Blight J, Lazaro Moreli M, Montoya-Diaz E, Huiskonen JT, et al. (April 2019). "Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus". Viruses. 11 (4): 322. doi: 10.3390/v11040322 . PMC   6521086 . PMID   30987160.
  12. 1 2 "Two groups of UK scientists in race to develop coronavirus vaccine". Evening Standard. 7 February 2020. Retrieved 27 March 2020.
  13. 1 2 "Vaccine trials among recipients of £20 million coronavirus research investment". GOV.UK. Retrieved 27 March 2020.
  14. ↑ "Oxford team to begin novel coronavirus vaccine research". University of Oxford. 7 February 2020.
  15. ↑ Lane R (April 2020). "Sarah Gilbert: carving a path towards a COVID-19 vaccine". Lancet. 395 (10232): 1247. doi:10.1016/S0140-6736(20)30796-0. PMC   7162644 . PMID   32305089.
  16. ↑ "COVID-19 Vaccine Trials | COVID-19". covid19vaccinetrial.co.uk. Retrieved 11 April 2020.
  17. ↑ Sample I (19 March 2020). "Trials to begin on Covid-19 vaccine in UK next month". The Guardian.
  18. ↑ Robson S (20 March 2020). "British scientists hope to start coronavirus vaccine trials next month". manchestereveningnews.co.uk. Retrieved 27 March 2020.
  19. ↑ Devlin H (27 March 2020). "UK scientists enrol volunteers for coronavirus vaccine trial". The Guardian.
  20. ↑ Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. (August 2020). "Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial". Lancet. 396 (10249): 467–478. doi:10.1016/S0140-6736(20)31604-4. hdl: 10044/1/81821 . PMC   7445431 . PMID   32702298. S2CID   220651577.
  21. ↑ Gallagher J, Triggle N (30 December 2020). "Covid-19: Oxford-AstraZeneca vaccine approved for use in UK". BBC News.

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