Wiki.RIP

Ebola vaccine

From Wikipedia, the free encyclopedia

Ebola vaccine
Study Participant Receives NIAID-GSK Candidate Ebola Vaccine (3).jpg
Candidate Ebola vaccine being given
Vaccine description
Target diseaseEbola virus
TypeAttenuated virus
Clinical data
Trade namesErvebo
License data
ATC code
Legal status
Legal status

Ebola vaccines are a number of vaccines to prevent Ebola that are either approved or in development. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019.[1][2] It had been used extensively in 2018–19 under a compassionate use protocol.[3] Several promising vaccine candidates have been shown to protect nonhuman primates (usually macaques) against lethal infection.[4][5][6]

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 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.[7]

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.[8][9] In November 2019, the European Commission granted a conditional marketing authorization.[10] The WHO prequalification came fewer than 48 hours later, making it the fastest vaccine prequalification process ever conducted by WHO.[11] In December 2019 it was approved for medical use in the United States.[1]

It was developed by the Public Health Agency of Canada, with development subsequently taken over by Merck Inc.[12] In October 2014, the Wellcome Trust, who was also one of the biggest UK founders,[13] announced the start of multiple trials in healthy volunteers in Europe, Gabon, Kenya, and the US.[14] 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.[15] The trial was temporarily halted in December 2014 due to possible adverse effects, but subsequently resumed.[16] 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.[17] On 31 July 2015, preliminary results of a Phase III trial in Guinea indicated that the vaccine appears to be "highly efficacious and safe."[18] 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.[19][20] 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.[21] 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.[22][23][24]

The approval was supported by a study conducted in Guinea during the 2014–2016 outbreak in individuals 18 years of age and older.[1] 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.[1] This noteworthy 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.[1] 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.[1] 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.[1]

In additional studies, antibody responses were assessed in 477 individuals in Liberia, approximately 500 individuals in Sierra Leone and approximately 900 individuals in Canada, Spain and the U.S.[1] The antibody responses among those in the study conducted in Canada, Spain and the U.S. were similar to those among individuals in the studies conducted in Liberia and Sierra Leone.[1]

The safety was assessed in approximately 15,000 individuals in Africa, Europe and North America.[1] 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.[1]

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.[22][23][24] However, the design of this study and the high efficacy of the vaccine were questioned.[25] In November 2019, the European Commission granted a conditional marketing authorization to Ervebo (Ebola Zaire Vaccine (rVSV∆G-ZEBOV-GP, live))[26] and the World Health Organization (WHO) prequalified an Ebola vaccine for the first time.[11]

In development

Vaccine Associated organisations Status
Chimp adenovirus 3 vectored glycoprotein (cAd3-EBO Z) GSK & NIAID Phase III Feb. 2016[7]
rVSV vectored glycoprotein (VSV-EBOV) Newlink Genetics & Merck In use[27][28][26][1]
Human adenovirus 5 vectored 2014 glycoprotein insert (Ad5-EBOV) BIT & CanSino Phase I complete[29]
Adenovirus 26 vectored glycoprotein / MVA-BN (Ad26.ZEBOV/​MVA-BN) Johnson & Johnson Phase I complete April, 2016[30][31]
HPIV-3 vectored glycoprotein Ministry of Health (Russia) Phase I planned[32]
Rabies vectored glycoprotein Thomas Jefferson University & NIAID Non-human primate challenge complete[33]
Purified glycoprotein Protein Sciences NHP challenge initiated[34]
Ebola ∆VP30 H2O2 treated University of Wisconsin Non-human primate challenge complete[35]

cAd3-EBO Z

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.[36] 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.[37] 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.[38][39] 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.[40][41] 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.[17][42]

Ad26.ZEBOV/MVA-BN

Johnson & Johnson developed an Ebola vaccine at its Janssen Pharmaceutica Company. The regimen consists of two vaccine components (first vaccine as prime, followed by a second vaccine as boost)[43] that are based on AdVac technology from Crucell Holland B.V., which is part of Janssen, and 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.[44] This product commenced Phase I clinical trial at the Jenner Institute in Oxford during January 2015.[45][46] 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[43] with the first trial commenced in Sierra Leone in October 2015.[47]

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,[48] and in November 2019, Janssen submitted a Marketing Authorization Application (MAA) to the EMA for approval of Ad26.ZEBOV and MVA-BN.[48][49]

Ebola GP vaccine

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[50] 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 postexposure while animals were viremic and clinically ill.[51] 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.[52] 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.[53] As of November 2014, further development by the team appeared unlikely due to lack of funding.[52][54]

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.[55]

Novel recombinant adenovirus type-5 vector-based Ebola vaccine

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.[29]

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.[56] The new vaccine relies on a strain of Ebola called EBOVΔVP30, which is unable to replicate.[35]

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.[57]

Ad5-EBOV

In 2017, the China Food and Drug Administration (CFDA) announced approval of an Ebola vaccine, co-developed by the military-backed Bioengineering Institute of the Chinese Academy of Military Medical Sciences and private drugmaker Tianjin CanSino Biotechnology Inc.[58] It contains a human adenovirus serotype 5 vector (Ad5) with the glycoprotein gene from ZEBOV.[59] Their findings were consistent with previous tests on rVSV-ZEBOV in Africa and Europe.[60]

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.[61]

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 3 groups – members of the first two groups would receive the two candidate vaccines, while the third group will receive a placebo.[62] 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,[17][42] and in Guinea in March 2016.[20]

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.[15]

The Russian Foreign Ministry announced in 2016, the intention to conduct field trials of two Russian vaccines involving 2000 people.[63] 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.[63][64] As of October 2019, Russia licensed the vaccine and was reportedly ready to ship vaccine to Africa.[65]

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.[66] Congress passed a law in 2004, that funds a national stockpile of vaccines and medicine for possible outbreaks of disease.[66] A number of companies were expected to develop Ebola vaccines: GlaxoSmithKline, NewLink Genetics, Johnson & Johnson and Bavarian Nordic.[66] 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.[67] Supplies of ZMapp ran out in August 2014.[68] 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.[69] Additional contracts were signed in 2017.[70]

See also

References

  1. ^ a b c d e f g h i j k l "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). 19 December 2019. Archived from the original on 20 December 2019. Retrieved 19 December 2019. This article incorporates text from this source, which is in the public domain.
  2. ^ McKee S (23 December 2019). "US approves Merck's Ebola vaccine". PharmaTimes Online. Surrey, England: PharmaTimes Media Limited. Retrieved 24 December 2019.
  3. ^ "As Ebola outbreak rages, vaccine is 97.5% effective, protecting over 90K people". 16 April 2019.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ a b 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.
  8. ^ 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" (PDF). The Journal of Infectious Diseases. 214 (suppl 3): S360–66. doi:10.1093/infdis/jiw218. PMC 5050468. PMID 27496978.
  9. ^ 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.
  10. ^ "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.
  11. ^ a b "WHO prequalifies Ebola vaccine, paving the way for its use in high-risk countries". World Health Organization (WHO) (Press release). 12 November 2019. Archived from the original on 15 November 2019. Retrieved 13 November 2019.
  12. ^ "Canadian Ebola vaccine development taken over by Merck". CBC News. 24 November 2014. Retrieved 25 November 2014.
  13. ^ 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.
  14. ^ "Multiple trials of VSV Ebola vaccine accelerated by international collaborative" (Press release). Wellcome Trust. Retrieved 29 October 2014.
  15. ^ a b 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.
  16. ^ Chan M. "WHO Director-General opens high-level meeting on Ebola vaccines". World Health Organization (WHO). Retrieved 10 January 2015.
  17. ^ a b c "Ebola test vaccines appear safe in Phase 2 Liberian clinical trial" (Press release). National Institutes of Health (NIH). 26 March 2015.
  18. ^ 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.
  19. ^ "Ebola update (93): Positive vaccine trial results". ProMED mail. International Society for Infectious Diseases. Retrieved 2 August 2015.
  20. ^ a b "WHO coordinating vaccination of contacts to contain Ebola flare-up in Guinea". World Health Organization (WHO). March 2016. Retrieved 14 May 2016.
  21. ^ "World on the verge of an effective Ebola vaccine" (Press release). World Health Organization (WHO). 31 July 2015.
  22. ^ a b 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.
  23. ^ a b Berlinger J (22 December 2016). "Ebola vaccine gives 100% protection, study finds". CNN. Retrieved 27 December 2016.
  24. ^ a b "Final trial results confirm Ebola vaccine provides high protection against disease". World Health Organization (WHO) (Press release). 23 December 2016. Archived from the original on 11 November 2019. Retrieved 11 November 2019.
  25. ^ 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.
  26. ^ a b "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.
  27. ^ "WHO coordinating vaccination of contacts to contain Ebola flare-up in Guinea". World Health Organization (WHO). Retrieved 20 July 2016.
  28. ^ "Vaccines alliance signs $5 million advance deal for Merck's Ebola shot". Reuters. 20 January 2016. Retrieved 20 July 2016.
  29. ^ a b 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.
  30. ^ Clinical trial number NCT02313077 for "A Safety and Immunogenicity Study of Heterologous Prime-Boost Ebola Vaccine Regimens in Healthy Participants" at ClinicalTrials.gov
  31. ^ 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.
  32. ^ "Ebola vaccines, therapies, and diagnostics". World Health Organization (WHO). 6 July 2015. Retrieved 10 September 2015.
  33. ^ 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.
  34. ^ "CT lab hopes to stop spread of Ebola". 3 March 2015. Retrieved 10 September 2015.
  35. ^ a b 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.
  36. ^ Vaccine Research Center, NIAID (2 October 2014). "Ebola Vaccine Clinical Development Overview (presentation)" (PDF). World Health Organization (WHO). Retrieved 21 October 2014.
  37. ^ Clinical trial number NCT02344407 for "Partnership for Research on Ebola Vaccines in Liberia (PREVAIL)" at ClinicalTrials.gov
  38. ^ 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.
  39. ^ 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.
  40. ^ Clinical trial number NCT02240875 for "A Study to Assess New Ebola Vaccines, cAd3-EBO Z and MVA-BN Filo" at ClinicalTrials.gov
  41. ^ University of Oxford (4 December 2014). "Booster Ebola vaccine enters first trials at Oxford University". Retrieved 7 December 2014.
  42. ^ a b "Ebola vaccine trial begins in Sierra Leone" (Press release). Centers for Disease Control and Prevention (CDC). 14 April 2015.
  43. ^ a b 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.
  44. ^ Clinical trial number NCT02313077 for "A Safety and Immunogenicity Study of Heterologous Prime-Boost Ebola Vaccine Regimens in Healthy Participants" at ClinicalTrials.gov
  45. ^ Walsh F (6 January 2015). "Ebola: New vaccine trial begins". BBC News Online. Retrieved 6 January 2015.
  46. ^ "Johnson & Johnson Announces Major Commitment to Speed Ebola Vaccine Development and Significantly Expand Production" (Press release). Johnson & Johnson. Retrieved 6 January 2015.
  47. ^ Hirschler B (9 October 2015). "J&J starts vaccine trial in Sierra Leone, even as Ebola fades". Reuters. Retrieved 15 October 2015.
  48. ^ a b "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.
  49. ^ 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.
  50. ^ 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.
  51. ^ 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.
  52. ^ a b Ackerman T (5 November 2014). "UT nasal spray vaccine for Ebola effective in monkeys". Houston Chronicle. Retrieved 13 November 2014.
  53. ^ 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.
  54. ^ Stanton D (12 November 2014). "Ebola nasal vaccine under threat as funding runs dry". in-PharmaTechnologist. Crawley, Sussex, UK: William Reed Business Media. Retrieved 13 November 2014.
  55. ^ "Vaxart Completes Financing to Fund Expanding Development Portfolio". Vaxart. Archived from the original on 19 January 2015. Retrieved 19 January 2015.
  56. ^ 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.
  57. ^ 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.
  58. ^ Feng C (20 October 2017). "China Approves Ebola Vaccine". Caixin Global. Archived from the original on 7 October 2018. Retrieved 7 October 2018.
  59. ^ 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.
  60. ^ Hackett DW (31 March 2018). "Ebola Vaccine Development Race Between the USA and China". Precision Vaccinations.
  61. ^ 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.
  62. ^ "UK leads promising Ebola vaccine trial Pharmaceutical company looking into largescale manufacturing if trials are successful". Ars Technica. Retrieved 10 January 2015.
  63. ^ a b "Russia to fund Ebola vaccine trials". Retrieved 14 September 2017.
  64. ^ "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). Retrieved 14 September 2017.
  65. ^ "Russia ready to supply Ebola vaccine to Africa". TASS. Retrieved 1 November 2019.
  66. ^ a b c Rooney B (28 October 2014). "Ebola: The making of a $1 billion drug". CNN. Retrieved 19 November 2014.
  67. ^ Gantz S (20 October 2014). "Emergent BioSolutions among three under consideration for Ebola drug manufacturing". Baltimore Business Journal. Retrieved 13 November 2014.
  68. ^ Bernstein L, Dennis B (11 August 2014). "Ebola test drug's supply 'exhausted' after shipments to Africa, U.S. company says". The Washington Post. Retrieved 17 November 2019.
  69. ^ 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.
  70. ^ "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

External links

What is Wiki.RIP There is a free information resource on the Internet. It is open to any user. Wiki is a library that is public and multilingual.

The basis of this page is on Wikipedia. Text licensed under CC BY-SA 3.0 Unported License..

Wikipedia® is a registered trademark of Wikimedia Foundation, Inc. wiki.rip is an independent company that is not affiliated with the Wikimedia Foundation (Wikimedia Foundation).

E-mail: wiki@wiki.rip
WIKI OPPORTUNITIES
Privacy Policy      Terms of Use      Disclaimer