Ebola vaccine

Last updated

Ebola vaccine
Study Participant Receives NIAID-GSK Candidate Ebola Vaccine (3).jpg
Candidate Ebola vaccine being given
Vaccine description
Target Ebola virus
Vaccine type Viral vector
Clinical data
Trade names Ervebo, Zabdeno, Mvabea
ATC code
Legal status
Legal status
Identifiers
CAS Number

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. [8] [9] It had been used extensively in the Kivu Ebola epidemic under a compassionate use protocol. [10] During the early 21st century, several vaccine candidates displayed efficacy to protect nonhuman primates (usually macaques) against lethal infection. [11] [12] [13]

Contents

Vaccines include replication-deficient adenovirus vectors, replication-competent vesicular stomatitis (VSV) and human parainfluenza (HPIV-3) vectors, and virus-like nanoparticle preparations. Conventional trials to study efficacy by exposure of humans to the pathogen after immunization are not ethical in this case. For such situations, the US Food and Drug Administration (FDA) has established the "animal efficacy rule" allowing licensure to be approved on the basis of animal model studies that replicate human disease, combined with evidence of safety and a potentially potent immune response (antibodies in the blood) from humans given the vaccine. Clinical trials involve the administration of the vaccine to healthy human subjects to evaluate the immune response, identify any side effects and determine the appropriate dosage. [14]

Approved

rVSV-ZEBOV

VSV-EBOV or rVSV-ZEBOV, sold under the brand name Ervebo, is a vaccine based on the vesicular stomatitis virus which was genetically modified to express a surface glycoprotein of Zaire Ebola virus. [15] [16] In November 2019, the European Commission granted a conditional marketing authorization. [17] The WHO prequalification came fewer than 48 hours later, making it the fastest vaccine prequalification process ever conducted by WHO. [18] It was approved for medical use in the European Union in November 2019. [3] It was approved for medical use in the United States in December 2019. [8] [2]

The most common side effects include pain, swelling and redness at the injection site, headache, fever, muscle pain, tiredness and joint pain. [3] In general, these reactions occur within seven days after vaccination, are mild to moderate in intensity and resolved in less than a week. [3]

It was developed by the Public Health Agency of Canada, with development subsequently taken over by Merck Inc. [19] In October 2014, the Wellcome Trust, who was also one of the biggest UK founders, [20] announced the start of multiple trials in healthy volunteers in Europe, Gabon, Kenya, and the US. [21] The vaccine was proven safe at multiple sites in North America, Europe, and Africa, but several volunteers at one trial site in Geneva, Switzerland, developed vaccine-related arthritis after about two weeks, and about 20–30% of volunteers at reporting sites developed low-grade post-vaccine fever, which resolved within a day or two. Other common side-effects were pain at the site of injection, myalgia, and fatigue. [22] The trial was temporarily halted in December 2014 due to possible adverse effects, but subsequently resumed. [23] As of April 2015, a Phase III trial with a single dose of VSV-EBOV began in Liberia after a successful Phase II study in the West African country. [24] On 31 July 2015, preliminary results of a Phase III trial in Guinea indicated that the vaccine appeared to be "highly efficacious and safe." [25] The trial used a ring vaccination protocol that first vaccinated all the closest contacts of new cases of Ebola infection either immediately or after 21 days. Because of the demonstrated efficacy of immediate vaccination, all recipients will now be immunized immediately. [26] [27] Ring vaccination is the method used in the program to eradicate smallpox in the 1970s. The trial will continue to assess whether the vaccine is effective in creating herd immunity to Ebola virus infection. [28] In December 2016, a study found the VSV-EBOV vaccine to be 95–100% effective against the Ebola virus, making it the first proven vaccine against the disease. [29] [30] [31]

The approval was supported by a study conducted in Guinea during the 2014–2016 outbreak in individuals 18 years of age and older. [8] The study was a randomized cluster (ring) vaccination study in which 3,537 contacts, and contacts of contacts, of individuals with laboratory-confirmed Ebola virus disease (EVD) received either "immediate" or 21-day "delayed" vaccination. [8] This design was intended to capture a social network of individuals and locations that might include dwellings or workplaces where a patient spent time while symptomatic, or the households of individuals who had contact with the patient during that person's illness or death. [8] In a comparison of cases of EVD among 2,108 individuals in the "immediate" vaccination arm and 1,429 individuals in the "delayed" vaccination arm, Ervebo was determined to be 100% effective in preventing Ebola cases with symptom onset greater than ten days after vaccination. [8] No cases of EVD with symptom onset greater than ten days after vaccination were observed in the "immediate" cluster group, compared with ten cases of EVD in the 21-day "delayed" cluster group. [8]

In additional studies, antibody responses were assessed in 477 individuals in Liberia, some 500 individuals in Sierra Leone, and about 900 individuals in Canada, Spain, and the US. [8] The antibody responses among those in the study conducted in Canada, Spain and the US were similar to those among individuals in the studies conducted in Liberia and Sierra Leone. [8]

The safety was assessed in approximately 15,000 individuals in Africa, Europe, and North America. [8] The most commonly reported side effects were pain, swelling and redness at the injection site, as well as headache, fever, joint and muscle aches and fatigue. [8]

In December 2016, a study found the VSV-EBOV vaccine to be 70–100% effective against the Ebola virus, making it the first proven vaccine against the disease. [29] [30] [31] However, the design of this study and the high efficacy of the vaccine were questioned. [32] In November 2019, the European Commission granted a conditional marketing authorization to Ervebo (rVSV∆G-ZEBOV-GP, live) [17] [33] [34] and the WHO prequalified an Ebola vaccine for the first time. [18]

In July 2023, the FDA expanded the indication for Ervebo to cover people aged 12 years of age and older. [35] [36]

Zabdeno/Mvabea

The two-dose regimen of Ad26.ZEBOV and MVA-BN-Filo, sold under the brand names Zabdeno and Mvabea, [4] [5] was developed by Johnson & Johnson at its Janssen Pharmaceutical company. It was approved for medical use in the European Union in July 2020. [37] [4] [5]

The regimen consists of two vaccine components (first vaccine as prime, followed by a second vaccine as boost) [38] – the first based on AdVac technology from Crucell Holland B.V. (which is part of Janssen), the second based on the MVA-BN technology from Bavarian Nordic. The Ad26.ZEBOV is derived from human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein, while the second component MVA-BN is the Modified Vaccinia Virus Ankara – Bavarian Nordic (MVA-BN) Filo-vector. [39] This product commenced Phase I clinical trial at the Jenner Institute in Oxford during January 2015. [40] [41] The preliminary data indicated the prime-boost vaccine regimen elicited temporary immunologic response in the volunteers as expected from vaccination. The Phase II trial enrolled 612 adult volunteers and commenced in July 2015, in the United Kingdom and France. A second Phase II trial, involving 1,200 volunteers, was initiated in Africa [38] with the first trial commenced in Sierra Leone in October 2015. [42]

In September 2019, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) granted an accelerated assessment to Janssen for Ad26.ZEBOV and MVA-BN-Filo, [43] and in November 2019, Janssen submitted a Marketing Authorization Application (MAA) to the EMA for approval of Ad26.ZEBOV and MVA-BN-Filo. [43] [44]

In May 2020, the EMA CHMP recommended granting a marketing authorization for the combination of Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea) vaccines. [45] [46] [47] Zabdeno is given first and Mvabea is administered approximately eight weeks later as a booster. [45] This prophylactic two-dose regimen is therefore not suitable for an outbreak response where immediate protection is necessary. [45] As a precautionary measure for individuals at imminent risk of exposure to Ebola virus (for example healthcare professionals and those living in or visiting areas with an ongoing Ebola virus disease outbreak), an extra Zabdeno booster vaccination should be considered for individuals who completed the Zabdeno-Mvabea two-dose vaccination regimen more than four months ago. [45] Efficacy for humans is not yet known as the efficacy has been extrapolated from animal studies. [48]

Ad5-EBOV

In late 2014 and early 2015, a double-blind, randomized Phase I trial was conducted in the Jiangsu Province of China; the trial examined a vaccine that contains glycoproteins of the 2014 strain, rather than those of the 1976 strain. The trial found signals of efficacy and raised no significant safety concerns. [49]

In 2017, the China Food and Drug Administration (CFDA) announced approval of an Ebola vaccine, co-developed by the Institute of Biotechnology of the Academy of Military Medical Sciences and the private vaccine-maker CanSino Biologics. [50] [51] It contains a human adenovirus serotype 5 vector (Ad5) with the glycoprotein gene from ZEBOV. [52] Their findings were consistent with previous tests on rVSV-ZEBOV in Africa and Europe. [53]

In development

VaccineAssociated organisationsStatus
Chimp adenovirus 3 vectored glycoprotein (cAd3-EBO Z) GSK & NIAID Phase III Feb. 2016 [14]
rVSV vectored glycoprotein (VSV-EBOV)Newlink Genetics & Merck In use [54] [55] [17] [8]
Adenovirus 26 vectored glycoprotein / MVA-BN (Ad26.ZEBOV/​MVA-BN) Johnson & Johnson In use [39] [56]
HPIV-3 vectored glycoprotein Ministry of Health (Russia) Phase I planned [57]
Rabies vectored glycoprotein Thomas Jefferson University & NIAIDNon-human primate challenge complete [58]
Purified glycoprotein Protein Sciences NHP challenge initiated [59]
Ebola ∆VP30 H2O2 treated University of Wisconsin Non-human primate challenge complete [60]

cAd3-EBO Z

Ebola virions Ebola virions.png
Ebola virions

In September 2014, two Phase I clinical trials began for the vaccine cAd3-EBO Z, which is based on an attenuated version of a chimpanzee adenovirus (cAd3) that has been genetically altered so that it is unable to replicate in humans. [61] The cAd3 vector has a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion. [62] It was developed by NIAID in collaboration with Okairos, now a division of GlaxoSmithKline. For the trial designated VRC 20, 20 volunteers were recruited by the NIAID in Bethesda, Maryland, while three dose-specific groups of 20 volunteers each were recruited for trial EBL01 by University of Oxford, UK. Initial results were released in November 2014; all 20 volunteers developed antibodies against Ebola and there were no significant concerns raised about safety. [63] [64] In December 2014, University of Oxford expanded the trial to include a booster vaccine based on MVA-BN, a strain of Modified vaccinia Ankara, developed by Bavarian Nordic, to investigate whether it can help increase immune responses further. [65] [66] The trial which has enrolled a total of 60 volunteers will see 30 volunteers vaccinated with the booster vaccine. As of April 2015, Phase III trial with a single dose of cAd3-EBO Z begins in Sierra Leone after a successful Phase 2 study in West Africa countries. [24] [67]

Ebola GP vaccine

Recombinant formation plasmids Recombinant formation of plasmids.svg
Recombinant formation plasmids

At the 8th Vaccine and ISV Conference in Philadelphia on 27−28 October 2014, Novavax Inc. reported the development in a "few weeks" of a glycoprotein (GP) nanoparticle Ebola virus (EBOV GP) vaccine using their proprietary recombinant technology. A recombinant protein is a protein whose code is carried by recombinant DNA. The vaccine is based on the newly published genetic sequence [68] of the 2014 Guinea Ebola (Makona) strain that is responsible for the 2014 Ebola disease epidemic in West Africa. In animal studies, a useful immune response was induced and was found to be enhanced ten to a hundred-fold by the company's "Matrix-M" immunologic adjuvant. A study of the response of non-human primate to the vaccine had been initiated. As of February 2015, Novavax had completed two primate studies on baboons and macaques and had initiated a Phase I clinical trial in Australia. The Lipid nanoparticle (LNP)-encapsulated siRNAs rapidly adapted to target the Makona outbreak strain of EBOV and are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at three days post-exposure while animals were viremic and clinically ill. [69] The top line Phase I human trial results showed that the adjuvanted Ebola GP Vaccine was highly immunogenic at all dose levels.[ medical citation needed ]

Nasal vaccine

On 5 November 2014, the Houston Chronicle reported that a research team at the University of Texas-Austin was developing a nasal spray Ebola vaccine, which the team had been working on for seven years. [70] The team reported in 2014, that in the nonhuman primate studies it conducted, the vaccine had more efficacy when delivered via nasal spray than by injection. [71] As of November 2014, further development by the team appeared unlikely due to lack of funding. [70] [72]

Vaxart tablet

Vaxart Inc. is developing a vaccine technology in the form of a temperature-stable tablet which may offer advantages such as reduced cold chain requirement, and rapid and scalable manufacturing. In January 2015, Vaxart announced that it had secured funding to develop its Ebola vaccine to Phase I trial. [73]

Attenuated Ebola virus vaccine

A study published in Science during March 2015, demonstrated that vaccination with a weakened form of the Ebola virus provides some measure of protection to non-human primates. This study was conducted in accordance with a protocol approved by an Institutional Animal Care and Use Committee of the National Institutes of Health. [74] The new vaccine relies on a strain of Ebola called EBOVΔVP30, which is unable to replicate. [60]

GamEvac-Combi

A study published in Human Vaccines & Immunotherapeutics in March 2017, analyzing data from a clinical trial of the GamEvac-Combi vaccine in Russia, concluded said vaccine to be safe and effective and recommended proceeding to Phase III trials. [75]

Prospects

In September 2019, a study published in Cell Reports demonstrated the role of the Ebola virus VP35 protein in its immune evasion. A recombinant form of Ebola virus with a mutant VP35 protein (VP35m) was developed, and showed positive results in the activation of the RIG-I-like receptor signaling. Non-human primates were challenged with different doses of VP35. This challenge resulted in the activation of the innate immune system and the production of anti-EBOV antibodies. The primates were then back-challenged with the wild type Ebola virus and survived. This potentially creates a prospect for a future vaccine development. [76]

Clinical trials in West Africa

In January 2015, Marie-Paule Kieny, the World Health Organization's (WHO) assistant director-general of health systems and innovation, announced that the vaccines cAd3-EBO Z and VSV-EBOV had demonstrated acceptable safety profiles during early testing and would soon progress to large-scale trials in Liberia, Sierra Leone, and Guinea. The trials would involve up to 27,000 people and comprise three groups – members of the first two groups would receive the two candidate vaccines, while the third group will receive a placebo. [77] Both vaccines have since successfully completed the Phase 2 studies. The large scale Phase 3 studies have begun as of April 2015, in Liberia and Sierra Leone, [24] [67] and in Guinea in March 2016. [27]

In addition, a medical anthropologist at Université de Montréal, had been working in Guinea and raised further questions about safety in the ring trial after spending time in April at one of the Ebola treatment units where trial participants are taken if they become ill, the centre in Coyah, about 50 km from the capital of Conakry. [22]

The Russian Foreign Ministry announced in 2016, the intention to conduct field trials of two Russian vaccines involving 2000 people. [78] According to local media reports, the Guinean government authorized the commencement of the trials on 9 August 2017, at the Rusal-built Research and Diagnostic Center of Epidemiology and Microbiology in Kindia. The trials were slated to continue until 2018. [78] [79] As of October 2019, Russia licensed the vaccine by local regulatory authorities and was reportedly ready to ship vaccine to Africa. [80]

U.S. national stockpile

In 2014, Credit Suisse estimated that the U.S. government will provide over $1 billion in contracts to companies to develop medicine and vaccines for Ebola virus disease. [81] Congress passed a law in 2004 that funds a national stockpile of vaccines and medicine for possible outbreaks of disease. [81] A number of companies were expected to develop Ebola vaccines: GlaxoSmithKline, NewLink Genetics, Johnson & Johnson, and Bavarian Nordic. [81] Another company, Emergent BioSolutions, was a contestant for manufacturing new doses of ZMapp,[ citation needed ] a drug for Ebola virus disease treatment originally developed by Mapp Biopharmaceutical. [82] Supplies of ZMapp ran out in August 2014. [83] In September 2014, the Biomedical Advanced Research and Development Authority (BARDA) entered into a multimillion-dollar contract with Mapp Biopharmaceutical to accelerate the development of ZMapp. [84] Additional contracts were signed in 2017. [85]

See also

Related Research Articles

<i>Indiana vesiculovirus</i> Species of virus

Indiana vesiculovirus, formerly Vesicular stomatitis Indiana virus is a virus in the family Rhabdoviridae; the well-known Rabies lyssavirus belongs to the same family. VSIV can infect insects, cattle, horses and pigs. It has particular importance to farmers in certain regions of the world where it infects cattle. This is because its clinical presentation is identical to the very important foot and mouth disease virus.

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.

The United States Military HIV Research Program was initiated by the United States Congress in 1986, in reaction to the threat of lost effectiveness of U.S./Allied troops due to HIV infection. The mission of MHRP is to develop an HIV-1 vaccine, provide prevention, care, and treatment, and conduct meaningful HIV/AIDS research for the global community through the President's Emergency Plan for AIDS Relief (PEPFAR). It is centered at the Walter Reed Army Institute of Research (WRAIR), and has established five international research sites in Africa and Asia. MHRP also partners with the Armed Forces Research Institute of Medical Sciences (AFRIMS) in Thailand. MHRP works closely with The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), most notably in the development of the RV144 HIV vaccine in Thailand. MHRP is the largest research program supported by the HJF.

The species Sudan ebolavirus is a virological taxon included in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The species has a single virus member, Sudan virus (SUDV). The members of the species are called Sudan ebolaviruses. It was discovered in 1977 and causes Ebola clinically indistinguishable from the ebola Zaire strain, but is less transmissible than it. Unlike with ebola Zaire there is no vaccine available.

<span class="mw-page-title-main">Ebola</span> Viral hemorrhagic fever of humans and other primates caused by ebolaviruses

Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after infection. The first symptoms are usually fever, sore throat, muscle pain, and headaches. These are usually followed by vomiting, diarrhoea, rash and decreased liver and kidney function, at which point some people begin to bleed both internally and externally. It kills between 25% and 90% of those infected – about 50% on average. Death is often due to shock from fluid loss, and typically occurs between six and 16 days after the first symptoms appear. Early treatment of symptoms increases the survival rate considerably compared to late start. An Ebola vaccine was approved by the US FDA in December 2019.

<i>Zaire ebolavirus</i> Species of virus affecting humans and animals

Zaire ebolavirus, more commonly known as Ebola virus, is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD). Ebola virus has caused the majority of human deaths from EVD, and was the cause of the 2013–2016 epidemic in western Africa, which resulted in at least 28,646 suspected cases and 11,323 confirmed deaths.

<span class="mw-page-title-main">ZMapp</span> Experimental treatment for Ebola virus disease

ZMapp is an experimental biopharmaceutical drug comprising three chimeric monoclonal antibodies under development as a treatment for Ebola virus disease. Two of the three components were originally developed at the Public Health Agency of Canada's National Microbiology Laboratory (NML), and the third at the U.S. Army Medical Research Institute of Infectious Diseases; the cocktail was optimized by Gary Kobinger, a research scientist at the NML and underwent further development under license by Mapp Biopharmaceutical. ZMapp was first used on humans during the Western African Ebola virus epidemic, having only been previously tested on animals and not yet subjected to a randomized controlled trial. The National Institutes of Health (NIH) ran a clinical trial starting in January 2015 with subjects from Sierra Leone, Guinea, and Liberia aiming to enroll 200 people, but the epidemic waned and the trial closed early, leaving it too statistically underpowered to give a meaningful result about whether ZMapp worked.

rVSV-ZEBOV vaccine Vaccine against Ebola virus disease

Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used in ring vaccination, rVSV-ZEBOV has shown a high level of protection. Around half the people given the vaccine have mild to moderate adverse effects that include headache, fatigue, and muscle pain.

cAd3-ZEBOV Experimental vaccine for ebolaviruses

cAd3-ZEBOV was an experimental vaccine for two ebolaviruses, Ebola virus and Sudan virus, developed by scientists at GlaxoSmithKline (GSK) and tested by National Institute of Allergy and Infectious Disease (NIAID). This vaccine is derived from a chimpanzee adenovirus, Chimp Adenovirus type 3 (ChAd3), genetically engineered to express glycoproteins from the Zaire and Sudan species of ebolavirus to provoke an immune response against them. Simultaneous phase 1 trials of this vaccine commenced in September 2014, being administered to volunteers in Oxford and Bethesda. During October the vaccine is being administered to a further group of volunteers in Mali. If this phase is completed successfully, the vaccine will be fast tracked for use in the Ebola virus epidemic in West Africa. In preparation for this, GSK is preparing a stockpile of 10,000 doses.

<span class="mw-page-title-main">Ebola virus disease treatment research</span>

There is a cure for the Ebola virus disease that is currently approved for market the US government has inventory in the Strategic National Stockpile. For past and current Ebola epidemics, treatment has been primarily supportive in nature.

<span class="mw-page-title-main">Ring vaccination</span> Strategy to inhibit the spread of a disease by vaccinating those most likely to be infected

Ring vaccination is a strategy to inhibit the spread of a disease by vaccinating those who are most likely to be infected.

<span class="mw-page-title-main">Universal flu vaccine</span> Vaccine that prevents infection from all strains of the flu

A universal flu vaccine is a flu vaccine that is effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift. Hence it should not require modification from year to year. As of 2021 no universal flu vaccine had been approved for general use, several were in development, and one was in clinical trial.

<span class="mw-page-title-main">2018 Équateur province Ebola outbreak</span> Disease outbreak in the Democratic Republic of the Congo

The 2018 Équateur province Ebola outbreak occurred in the north-west of the Democratic Republic of the Congo (DRC) from May to July 2018. It was contained entirely within Équateur province, and was the first time that vaccination with the rVSV-ZEBOV Ebola vaccine had been attempted in the early stages of an Ebola outbreak, with a total of 3,481 people vaccinated. It was the ninth recorded Ebola outbreak in the DRC.

Natalie E. Dean is an American biostatistician specializing in infectious disease epidemiology. Dean is currently an assistant professor of Biostatistics at the University of Florida. Her research involves epidemiological modeling of outbreaks, including Ebola, Zika and COVID-19.

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.

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.

<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.

Endothelial cell tropism or endotheliotropism is a type of tissue tropism or host tropism that characterizes an pathogen's ability to recognize and infect an endothelial cell. Pathogens, such as viruses, can target a specific tissue type or multiple tissue types. Like other cells, the endothelial cell possesses several features that supports a productive viral infection a cell including, cell surface receptors, immune responses, and other virulence factors. Endothelial cells are found in various tissue types such as in the capillaries, veins, and arteries in the human body. As endothelial cells line these blood vessels and critical networks that extend access to various human organ systems, the virus entry into these cells can be detrimental to virus spread across the host system and affect clinical course of disease. Understanding the mechanisms of how viruses attach, enter, and control endothelial functions and host responses inform infectious disease understanding and medical countermeasures.

Gary P. Kobinger is a Canadian immunologist and virologist who is currently the director at the Galveston National Laboratory at the University of Texas. He has held previous professorships at Université Laval, the University of Manitoba, and the University of Pennsylvania. Additionally, he was the chief of the Special Pathogens Unit at the National Microbiology Laboratory (NML) of the Public Health Agency of Canada (PHAC) in Winnipeg, Manitoba, for eight years. Kobinger is known for his critical role in the development of both an effective Ebola vaccine and treatment. His work focuses on the development and evaluation of new vaccine platforms and immunological treatments against emerging and re-emerging viruses that are dangerous to human health.

References

  1. ↑ "Ervebo (zaire ebolavirus- strain kikwit-95 envelope glycoprotein injection, solution". DailyMed. 13 December 2022. Archived from the original on 5 March 2023. Retrieved 4 March 2023.
  2. 1 2 "Ervebo". U.S. Food and Drug Administration (FDA). 19 December 2019. Archived from the original on 14 February 2021. Retrieved 1 July 2020.
  3. 1 2 3 4 "Ervebo EPAR". European Medicines Agency (EMA). 12 December 2019. Archived from the original on 8 March 2021. Retrieved 1 July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. 1 2 3 "Zabdeno EPAR". European Medicines Agency (EMA). 26 May 2020. Archived from the original on 23 July 2020. Retrieved 23 July 2020.
  5. 1 2 3 "Mvabea EPAR". European Medicines Agency (EMA). 26 May 2020. Archived from the original on 23 July 2020. Retrieved 23 July 2020.
  6. ↑ "Zabdeno Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  7. ↑ "Mvabea Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 "First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response". U.S. Food and Drug Administration (FDA) (Press release). 19 December 2019. Archived from the original on 20 December 2019. Retrieved 19 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ McKee S (23 December 2019). "US approves Merck's Ebola vaccine". PharmaTimes Online. Surrey, England: PharmaTimes Media Limited. Archived from the original on 25 January 2021. Retrieved 24 December 2019.
  10. ↑ Beth Mole (16 April 2019). "As Ebola outbreak rages, vaccine is 97.5% effective, protecting over 90K people". Ars Technica. Archived from the original on 19 February 2021. Retrieved 5 July 2019.
  11. ↑ Hoenen T, Groseth A, Feldmann H (July 2012). "Current ebola vaccines". Expert Opinion on Biological Therapy. 12 (7): 859–72. doi:10.1517/14712598.2012.685152. PMC   3422127 . PMID   22559078.
  12. ↑ Peterson AT, Bauer JT, Mills JN (January 2004). "Ecologic and geographic distribution of filovirus disease". Emerging Infectious Diseases. 10 (1): 40–47. doi:10.3201/eid1001.030125. PMC   3322747 . PMID   15078595.
  13. ↑ Fausther-Bovendo H, Mulangu S, Sullivan NJ (June 2012). "Ebolavirus vaccines for humans and apes". Current Opinion in Virology. 2 (3): 324–29. doi:10.1016/j.coviro.2012.04.003. PMC   3397659 . PMID   22560007.
  14. 1 2 Pavot V (December 2016). "Ebola virus vaccines: Where do we stand?". Clinical Immunology. 173: 44–49. doi:10.1016/j.clim.2016.10.016. PMID   27910805.
  15. ↑ Marzi A, Hanley PW, Haddock E, Martellaro C, Kobinger G, Feldmann H (October 2016). "Efficacy of Vesicular Stomatitis Virus-Ebola Virus Postexposure Treatment in Rhesus Macaques Infected With Ebola Virus Makona". The Journal of Infectious Diseases. 214 (suppl 3): S360–66. doi:10.1093/infdis/jiw218. PMC   5050468 . PMID   27496978.
  16. ↑ Marzi A, Robertson SJ, Haddock E, Feldmann F, Hanley PW, Scott DP, et al. (August 2015). "Ebola Vaccine. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain". Science. 349 (6249): 739–42. doi: 10.1126/science.aab3920 . PMID   26249231.
  17. 1 2 3 "Merck's Ervebo [Ebola Zaire Vaccine (rVSVΔG-ZEBOV-GP) live] Granted Conditional Approval in the European Union" (Press release). Merck. 11 November 2019. Archived from the original on 11 November 2019. Retrieved 11 November 2019– via Business Wire.
  18. 1 2 "WHO prequalifies Ebola vaccine, paving the way for its use in high-risk countries" (Press release). World Health Organization. 12 November 2019. Archived from the original on 15 November 2019. Retrieved 13 November 2019.
  19. ↑ "Canadian Ebola vaccine development taken over by Merck". CBC News. 24 November 2014. Archived from the original on 12 January 2021. Retrieved 25 November 2014.
  20. ↑ Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, et al. (August 2015). "Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial". Lancet. 386 (9996): 857–66. doi:10.1016/s0140-6736(15)61117-5. hdl: 10144/575218 . PMID   26248676. S2CID   40830730.
  21. ↑ "Multiple trials of VSV Ebola vaccine accelerated by international collaborative" (Press release). Wellcome Trust. Archived from the original on 14 March 2016. Retrieved 29 October 2014.
  22. 1 2 Shuchman M (May 2015). "Ebola vaccine trial in west Africa faces criticism". Lancet. 385 (9981): 1933–34. doi:10.1016/s0140-6736(15)60938-2. PMID   25979835. S2CID   40400570.
  23. ↑ Margaret C. "WHO Director-General opens high-level meeting on Ebola vaccines". World Health Organization (WHO). Archived from the original on 18 January 2015. Retrieved 10 January 2015.
  24. 1 2 3 "Ebola test vaccines appear safe in Phase 2 Liberian clinical trial" (Press release). National Institutes of Health (NIH). 26 March 2015. Archived from the original on 10 January 2021. Retrieved 16 April 2015.
  25. ↑ Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, et al. (August 2015). "Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial". Lancet. 386 (9996): 857–66. doi:10.1016/S0140-6736(15)61117-5. hdl: 10144/575218 . PMID   26248676. S2CID   40830730.
  26. ↑ "Ebola update (93): Positive vaccine trial results". ProMED mail. International Society for Infectious Diseases. Archived from the original on 4 March 2016. Retrieved 2 August 2015.
  27. 1 2 "WHO coordinating vaccination of contacts to contain Ebola flare-up in Guinea". World Health Organization (WHO). March 2016. Archived from the original on 18 April 2018. Retrieved 14 May 2016.
  28. ↑ "World on the verge of an effective Ebola vaccine" (Press release). World Health Organization (WHO). 31 July 2015. Archived from the original on 31 July 2015.
  29. 1 2 Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, et al. (February 2017). "Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)". Lancet. 389 (10068): 505–18. doi:10.1016/S0140-6736(16)32621-6. PMC   5364328 . PMID   28017403.
  30. 1 2 Berlinger J (22 December 2016). "Ebola vaccine gives 100% protection, study finds". CNN. Archived from the original on 27 December 2016. Retrieved 27 December 2016.
  31. 1 2 "Final trial results confirm Ebola vaccine provides high protection against disease" (Press release). World Health Organization. 23 December 2016. Archived from the original on 11 November 2019. Retrieved 11 November 2019.
  32. ↑ Metzger WG, Vivas-Martínez S (March 2018). "Questionable efficacy of the rVSV-ZEBOV Ebola vaccine". Lancet. 391 (10125): 1021. doi: 10.1016/S0140-6736(18)30560-9 . PMID   29565013.
  33. ↑ "First vaccine to protect against Ebola". European Medicines Agency (Press release). 18 October 2019. Retrieved 15 October 2021.
  34. ↑ "Ebola Zaire Vaccine (rVSV∆G-ZEBOV-GP, live)". Union Register of medicinal products. Archived from the original on 24 October 2021. Retrieved 15 October 2021.
  35. ↑ "FDA Roundup: July 28, 2023". U.S. Food and Drug Administration (Press release). 28 July 2023. Retrieved 4 August 2023.
  36. ↑ "U.S. FDA Approves Merck's Ervebo (Ebola Zaire Vaccine, Live) for Use in Children 12 Months of Age and Older". Merck (Press release). 3 August 2023. Retrieved 4 August 2023.
  37. ↑ "Johnson & Johnson Announces European Commission Approval for Janssen's Preventive Ebola Vaccine" (Press release). Johnson & Johnson. 1 July 2020. Retrieved 16 July 2020– via Reuters.
  38. 1 2 Bavarian Nordic (15 July 2015). "Bavarian Nordic announces that the Oxford Vaccines Group has initiated a Phase 2 study of the Ebola prime-boost vaccine regimen combining MVA-BN Filo and Janssen's Advac technology" (Press release). Copenhagen, Denmark: Bavarian Nordic. Retrieved 16 July 2015.
  39. 1 2 Clinical trial number NCT02313077 for "A Safety and Immunogenicity Study of Heterologous Prime-Boost Ebola Vaccine Regimens in Healthy Participants" at ClinicalTrials.gov
  40. ↑ Walsh F (6 January 2015). "Ebola: New vaccine trial begins". BBC News Online. Archived from the original on 6 January 2015. Retrieved 6 January 2015.
  41. ↑ "Johnson & Johnson Announces Major Commitment to Speed Ebola Vaccine Development and Significantly Expand Production" (Press release). Johnson & Johnson. Archived from the original on 8 January 2015. Retrieved 6 January 2015.
  42. ↑ Hirschler B (9 October 2015). "J&J starts vaccine trial in Sierra Leone, even as Ebola fades". Reuters. Archived from the original on 11 March 2016. Retrieved 15 October 2015.
  43. 1 2 "Johnson & Johnson Announces Submission of European Marketing Authorisation Applications for Janssen's Investigational Ebola Vaccine Regimen". Janssen. 17 November 2019. Archived from the original on 17 November 2019. Retrieved 16 November 2019.
  44. ↑ Harper R (12 November 2019). "EU Marketing Authorisation submitted for Ebola vaccine regimen". European Pharmaceutical Review. Archived from the original on 17 November 2019. Retrieved 16 November 2019.
  45. 1 2 3 4 "New vaccine for prevention of Ebola virus disease recommended approval in the European Union". European Medicines Agency (EMA) (Press release). 29 May 2020. Retrieved 29 May 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  46. ↑ "Zabdeno: Pending EC decision". European Medicines Agency (EMA). 29 May 2020. Archived from the original on 15 June 2020. Retrieved 29 May 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  47. ↑ "Mvabea: Pending EC decision". European Medicines Agency (EMA). 29 May 2020. Archived from the original on 15 June 2020. Retrieved 29 May 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  48. ↑ Czarska-Thorley D (29 May 2020). "New vaccine for prevention of Ebola virus disease recommended approval in the European Union". European Medicines Agency (EMA). Archived from the original on 10 June 2020. Retrieved 7 July 2020.
  49. ↑ Zhu FC, Hou LH, Li JX, Wu SP, Liu P, Zhang GR, et al. (June 2015). "Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial". Lancet. 385 (9984): 2272–79. doi: 10.1016/S0140-6736(15)60553-0 . PMID   25817373. S2CID   34636122.
  50. ↑ Feng C (20 October 2017). "China Approves Ebola Vaccine". Caixin Global. Archived from the original on 7 October 2018. Retrieved 7 October 2018.
  51. ↑ "Overview of candidate Ebola vaccines as of August 19, 2019" (PDF). Strategic Advisory Group of Experts . 19 August 2019. Archived (PDF) from the original on 16 September 2021. Retrieved 7 December 2021.
  52. ↑ Wong G, Mendoza EJ, Plummer FA, Gao GF, Kobinger GP, Qiu X (February 2018). "From bench to almost bedside: the long road to a licensed Ebola virus vaccine". Expert Opinion on Biological Therapy. 18 (2): 159–73. doi:10.1080/14712598.2018.1404572. PMC   5841470 . PMID   29148858.
  53. ↑ Hackett DW (31 March 2018). "Ebola Vaccine Development Race Between the USA and China". Precision Vaccinations. Archived from the original on 28 November 2020. Retrieved 7 October 2018.
  54. ↑ "WHO coordinating vaccination of contacts to contain Ebola flare-up in Guinea". World Health Organization (WHO). Archived from the original on 18 April 2018. Retrieved 20 July 2016.
  55. ↑ "Vaccines alliance signs $5 million advance deal for Merck's Ebola shot". Reuters. 20 January 2016. Archived from the original on 5 July 2019. Retrieved 20 July 2016.
  56. ↑ Milligan ID, Gibani MM, Sewell R, Clutterbuck EA, Campbell D, Plested E, et al. (April 2016). "Safety and Immunogenicity of Novel Adenovirus Type 26- and Modified Vaccinia Ankara-Vectored Ebola Vaccines: A Randomized Clinical Trial". JAMA. 315 (15): 1610–23. doi: 10.1001/jama.2016.4218 . PMID   27092831.
  57. ↑ "Ebola vaccines, therapies, and diagnostics". World Health Organization (WHO). 6 July 2015. Archived from the original on 14 October 2014. Retrieved 10 September 2015.
  58. ↑ Blaney JE, Marzi A, Willet M, Papaneri AB, Wirblich C, Feldmann F, et al. (30 May 2015). "Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine". PLOS Pathogens. 9 (5): e1003389. doi: 10.1371/journal.ppat.1003389 . PMC   3667758 . PMID   23737747.
  59. ↑ "CT lab hopes to stop spread of Ebola". 3 March 2015. Archived from the original on 21 August 2015. Retrieved 10 September 2015.
  60. 1 2 Marzi A, Halfmann P, Hill-Batorski L, Feldmann F, Shupert WL, Neumann G, et al. (April 2015). "Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates". Science. 348 (6233): 439–42. doi:10.1126/science.aaa4919. PMC   4565490 . PMID   25814063.
  61. ↑ Vaccine Research Center, NIAID (2 October 2014). "Ebola Vaccine Clinical Development Overview (presentation)" (PDF). World Health Organization (WHO). Archived (PDF) from the original on 21 October 2014. Retrieved 21 October 2014.
  62. ↑ Clinical trial number NCT02344407 for "Partnership for Research on Ebola Vaccines in Liberia (PREVAIL)" at ClinicalTrials.gov
  63. ↑ Ledgerwood JE, DeZure AD, Stanley DA, Coates EE, Novik L, Enama ME, et al. (March 2017). "Chimpanzee Adenovirus Vector Ebola Vaccine". The New England Journal of Medicine. 376 (10): 928–38. doi: 10.1056/NEJMoa1410863 . PMID   25426834.
  64. ↑ Stanley DA, Honko AN, Asiedu C, Trefry JC, Lau-Kilby AW, Johnson JC, et al. (October 2014). "Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge". Nature Medicine. 20 (10): 1126–29. doi:10.1038/nm.3702. PMID   25194571. S2CID   20712490.
  65. ↑ Clinical trial number NCT02240875 for "A Study to Assess New Ebola Vaccines, cAd3-EBO Z and MVA-BN Filo" at ClinicalTrials.gov
  66. ↑ University of Oxford (4 December 2014). "Booster Ebola vaccine enters first trials at Oxford University". Archived from the original on 21 December 2014. Retrieved 7 December 2014.
  67. 1 2 "Ebola vaccine trial begins in Sierra Leone" (Press release). U.S. Centers for Disease Control and Prevention (CDC). 14 April 2015.
  68. ↑ Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, et al. (September 2014). "Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak". Science. 345 (6202): 1369–72. Bibcode:2014Sci...345.1369G. doi:10.1126/science.1259657. PMC   4431643 . PMID   25214632.
  69. ↑ Thi EP, Mire CE, Lee AC, Geisbert JB, Zhou JZ, Agans KN, et al. (May 2015). "Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates". Nature. 521 (7552): 362–65. Bibcode:2015Natur.521..362T. doi:10.1038/nature14442. PMC   4467030 . PMID   25901685.
  70. 1 2 Ackerman T (5 November 2014). "UT nasal spray vaccine for Ebola effective in monkeys". Houston Chronicle . Archived from the original on 12 November 2014. Retrieved 13 November 2014.
  71. ↑ Choi JH, Jonsson-Schmunk K, Qiu X, Shedlock DJ, Strong J, Xu JX, et al. (August 2015). "A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection". Molecular Pharmaceutics. 12 (8): 2712–31. doi:10.1021/mp500646d. PMC   4525323 . PMID   25363619.
  72. ↑ Stanton D (12 November 2014). "Ebola nasal vaccine under threat as funding runs dry". in-PharmaTechnologist. Crawley, Sussex, UK: William Reed Business Media. Archived from the original on 28 August 2021. Retrieved 13 November 2014.
  73. ↑ "Vaxart Completes Financing to Fund Expanding Development Portfolio". Vaxart. Archived from the original on 19 January 2015. Retrieved 19 January 2015.
  74. ↑ Marzi A, Feldmann F, Geisbert TW, Feldmann H, Safronetz D (February 2015). "Vesicular stomatitis virus-based vaccines against Lassa and Ebola viruses". Emerging Infectious Diseases. 21 (2): 305–07. doi:10.3201/eid2102.141649. PMC   4313664 . PMID   25625358.
  75. ↑ Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Dzharullaeva AS, Tukhvatulina NM, Shcheblyakov DV, et al. (March 2017). "Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia". Human Vaccines & Immunotherapeutics. 13 (3): 613–20. doi:10.1080/21645515.2016.1238535. PMC   5360131 . PMID   28152326.
  76. ↑ Woolsey C, Menicucci AR, Cross RW, Luthra P, Agans KN, Borisevich V, et al. (September 2019). "A VP35 Mutant Ebola Virus Lacks Virulence but Can Elicit Protective Immunity to Wild-Type Virus Challenge". Cell Reports. 28 (12): 3032–46.e6. doi:10.1016/j.celrep.2019.08.047. PMC   6886687 . PMID   31533029.
  77. ↑ "UK leads promising Ebola vaccine trial Pharmaceutical company looking into largescale manufacturing if trials are successful". Ars Technica . 10 January 2015. Archived from the original on 11 January 2015. Retrieved 10 January 2015.
  78. 1 2 "Russia to fund Ebola vaccine trials". Archived from the original on 21 August 2020. Retrieved 14 September 2017.
  79. ↑ "Guinée: un vaccin trouvé et testé contre le virus Ebola – Afrique Sur 7 : actualité de notre Afrique et du monde". www.afrique-sur7.fr (in French). Archived from the original on 4 October 2017. Retrieved 14 September 2017.
  80. ↑ "Russia ready to supply Ebola vaccine to Africa". TASS. Archived from the original on 3 May 2021. Retrieved 1 November 2019.
  81. 1 2 3 Rooney B (28 October 2014). "Ebola: The making of a $1 billion drug". CNN . Archived from the original on 1 November 2014. Retrieved 19 November 2014.
  82. ↑ Gantz S (20 October 2014). "Emergent BioSolutions among three under consideration for Ebola drug manufacturing". Baltimore Business Journal . Archived from the original on 30 October 2014. Retrieved 13 November 2014.
  83. ↑ Bernstein L, Brady D (11 August 2014). "Ebola test drug's supply 'exhausted' after shipments to Africa, U.S. company says". The Washington Post . Archived from the original on 17 November 2019. Retrieved 17 November 2019.
  84. ↑ McCarthy M (September 2014). "US signs contract with ZMapp maker to accelerate development of the Ebola drug". BMJ. 349 (sep04 10): g5488. doi: 10.1136/bmj.g5488 . PMID   25189475.
  85. ↑ "MappBio Announces Contracts with BARDA for ZMapp and Additional Filovirus Medical Countermeasures" (Press release). Mapp Biopharmaceutical. 29 September 2017. Archived from the original on 17 November 2019. Retrieved 16 November 2019.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.