Marburg vaccine

A Marburg vaccine would protect against Marburg virus disease (MVD). There are currently no Food and Drug Administration-approved vaccines for the prevention of MVD. Many candidate vaccines have been developed and tested in various animal models.^[1][2][3] There is not yet an approved vaccine, because of economic factors in vaccine development, and because filoviruses killed few before the 2010s.^[4]

The most promising candidate vaccines are DNA vaccines^[5] or based on Venezuelan equine encephalitis virus replicons,^[6] vesicular stomatitis Indiana virus (VSIV)^[2][7] or filovirus-like particles (VLPs)^[3] as all of these candidates could protect nonhuman primates from marburgvirus-induced disease. DNA vaccines have entered clinical trials.^[8]

History

The first clinical study testing the efficacy of a Marburg virus vaccine was conducted in 2014. The study tested a DNA vaccine and concluded that individuals inoculated with the vaccine exhibited some level of antibodies. However, these vaccines were not expected to provide definitive immunity.^[9] Several animal models have shown to be effective in the research of Marburg virus, such as hamsters, mice, and non-human primates (NHPs). Mice are useful in the initial phases of vaccine development as they are ample models for mammalian disease, but their immune systems are still different enough from humans to warrant trials with other mammals.^[10] Of these models, the infection in macaques seems to be the most similar to the effects in humans.^[11] A variety of other vaccines have been considered. Virus replicon particles (VRPs) were shown to be effective in guinea pigs, but lost efficacy once tested on NHPs. Additionally, an inactivated virus vaccine proved ineffective. DNA vaccines showed some efficacy in NHPs, but all inoculated individuals showed signs of infection.^[12]

Because Marburg virus and Ebola virus belong to the same family, Filoviridae, some scientists have attempted to create a single-injection vaccine for both viruses. This would both make the vaccine more practical and lower the cost for developing countries.^[13] Using a single-injection vaccine has shown to not cause any adverse reactogenicity, which the possible immune response to vaccination, in comparison to two separate vaccinations.^[9]

There is a candidate vaccine against the Marburg virus called rVSV-MARV. It was developed alongside vaccines for closely-related Ebolaviruses by the Canadian government in the early 2000s, twenty years before the outbreak. Production and testing of rVSV-MARV is blocked by legal monopolies held by the Merck Group. Merck acquired rights to all the closely-related candidate vaccines in 2014, but declined to work on most of them, including the Marburg vaccine, for economic reasons. While Merck returned the rights to the abandoned vaccines to the Public Health Agency of Canada, the vital rVSV vaccine production techniques which Merck had gained (while bringing the closely-related rVSV-ZEBOV vaccine into commercial use in 2019, with GAVI funding) remain Merck's, and cannot be used by anyone else wishing to develop a rVSV vaccine.^{[14][15][16][17]}

As of June 23, 2022, researchers working with the Public Health Agency of Canada conducted a study which showed promising results of a recombinant vesicular stomatitis virus (rVSV) vaccine in guinea pigs, entitled PHV01. According to the study, inoculation with the vaccine approximately one month prior to infection with the virus provided a high level of protection.^[18]

Even though there is much experimental research on Marburg virus, there is still no prominent vaccine. Human vaccination trials are either ultimately unsuccessful or are missing data specifically regarding Marburg virus.^[19] Due to the cost needed to handle Marburg virus at qualified facilities, the relatively few number of fatalities, and lack of commercial interest, the possibility of a vaccine has simply not come to fruition^[4] (see also economics of vaccines).

See also

• Rwanda Marburg virus disease outbreak

References

1. Garbutt, M.; Liebscher, R.; Wahl-Jensen, V.; Jones, S.; Möller, P.; Wagner, R.; Volchkov, V.; Klenk, H. D.; Feldmann, H.; Ströher, U. (2004). "Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses". Journal of Virology. 78 (10): 5458–5465. doi:10.1128/JVI.78.10.5458-5465.2004. PMC 400370. PMID 15113924.
2. Daddario-Dicaprio, K. M.; Geisbert, T. W.; Geisbert, J. B.; Ströher, U.; Hensley, L. E.; Grolla, A.; Fritz, E. A.; Feldmann, F.; Feldmann, H.; Jones, S. M. (2006). "Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine". Journal of Virology. 80 (19): 9659–9666. doi:10.1128/JVI.00959-06. PMC 1617222. PMID 16973570.
3. Swenson, D. L.; Warfield, K. L.; Larsen, T.; Alves, D. A.; Coberley, S. S.; Bavari, S. (2008). "Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses". Expert Review of Vaccines. 7 (4): 417–429. doi:10.1586/14760584.7.4.417. PMID 18444889. S2CID 23200723.
4. Reynolds P, Marzi A (August 2017). "Ebola and Marburg virus vaccines". Virus Genes. 53 (4): 501–515. doi:10.1007/s11262-017-1455-x. PMC 7089128. PMID 28447193.
5. Riemenschneider, J.; Garrison, A.; Geisbert, J.; Jahrling, P.; Hevey, M.; Negley, D.; Schmaljohn, A.; Lee, J.; Hart, M. K.; Vanderzanden, L.; Custer, D.; Bray, M.; Ruff, A.; Ivins, B.; Bassett, A.; Rossi, C.; Schmaljohn, C. (2003). "Comparison of individual and combination DNA vaccines for B. Anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus". Vaccine. 21 (25–26): 4071–4080. doi:10.1016/S0264-410X(03)00362-1. PMID 12922144. Archived (PDF) from the original on 2021-08-28. Retrieved 2019-06-29.
6. Hevey, M.; Negley, D.; Pushko, P.; Smith, J.; Schmaljohn, A. (Nov 1998). "Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates". Virology. 251 (1): 28–37. doi:10.1006/viro.1998.9367. ISSN 0042-6822. PMID 9813200.
7. Jones, M.; Feldmann, H.; Ströher, U.; Geisbert, J. B.; Fernando, L.; Grolla, A.; Klenk, H. D.; Sullivan, N. J.; Volchkov, V. E.; Fritz, E. A.; Daddario, K. M.; Hensley, L. E.; Jahrling, P. B.; Geisbert, T. W. (2005). "Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses". Nature Medicine. 11 (7): 786–790. doi:10.1038/nm1258. PMID 15937495. S2CID 5450135.
8. "Ebola/Marburg Vaccine Development" (Press release). National Institute of Allergy and Infectious Diseases. 2008-09-15. Archived from the original on 2010-03-06.
9. Kibuuka H, Berkowitz NM, Millard M, Enama ME, Tindikahwa A, Sekiziyivu AB, et al. (April 2015). "Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial". Lancet. 385 (9977): 1545–1554. doi:10.1016/S0140-6736(14)62385-0. PMID 25540891. S2CID 205975536.
10. Shifflett K, Marzi A (December 2019). "Marburg virus pathogenesis - differences and similarities in humans and animal models". Virology Journal. 16 (1): 165. doi:10.1186/s12985-019-1272-z. PMC 6937685. PMID 31888676.
11. Ewers EC, Pratt WD, Twenhafel NA, Shamblin J, Donnelly G, Esham H, et al. (March 2016). "Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques". Viruses. 8 (4): 87. doi:10.3390/v8040087. PMC 4848582. PMID 27043611.
12. Suschak JJ, Schmaljohn CS (2019-10-03). "Vaccines against Ebola virus and Marburg virus: recent advances and promising candidates". Human Vaccines & Immunotherapeutics. 15 (10): 2359–2377. doi:10.1080/21645515.2019.1651140. PMC 6816442. PMID 31589088.
13. Geisbert TW, Geisbert JB, Leung A, Daddario-DiCaprio KM, Hensley LE, Grolla A, Feldmann H (July 2009). "Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus". Journal of Virology. 83 (14): 7296–7304. doi:10.1128/JVI.00561-09. PMC 2704787. PMID 19386702.
14. "MSF's response to CEPI's policy regarding equitable access". Médecins Sans Frontières Access Campaign. September 25, 2018. Archived from the original on March 21, 2021. Retrieved April 10, 2020. In vaccine development, access to know how is important. Knowledge and expertise including but not limited to purification techniques, cell lines, materials, software codes and their transfer of this to alternative manufacturers in the event the awardee discontinues development of a promising vaccine is critically important. The recent example of Merck abandoning the development of rVSV vaccines for Marburg (rVSV-MARV) and for Sudan-Ebola (rVSV-SUDV) is a case in point. Merck continues to retain vital know-how on the rVSV platform as it developed the rVSV vaccine for Zaire-Ebola (rVSV-ZEBOV) with funding support from GAVI. While it has transferred the rights on these vaccines back to Public Health Agency of Canada, there is no mechanism to share know how on the rVSV platform with other vaccine developers who would like to also use rVSV as a vector against other pathogens.
15. "Merck & Co. Licenses NewLink's Ebola Vaccine Candidate". Genetic Engineering & Biotechnology News. November 24, 2014. Archived from the original on May 18, 2018. Retrieved January 20, 2016.
16. "Canadian Ebola vaccine development taken over by Merck". Reuters. November 24, 2014. Archived from the original on April 2, 2018. Retrieved January 10, 2020.
17. "First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response" (Press release). U.S. Food and Drug Administration (FDA). December 19, 2019. Archived from the original on December 20, 2019. Retrieved December 19, 2019. This article incorporates text from this source, which is in the public domain.
18. Zhu W, Liu G, Cao W, He S, Leung A, Ströher U, et al. (June 2022). "A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease". Vaccines. 10 (7): 1004. doi:10.3390/vaccines10071004. PMC 9324024. PMID 35891170.
19. Dulin N, Spanier A, Merino K, Hutter JN, Waterman PE, Lee C, Hamer MJ (January 2021). "Systematic review of Marburg virus vaccine nonhuman primate studies and human clinical trials". Vaccine. 39 (2): 202–208. doi:10.1016/j.vaccine.2020.11.042. PMID 33309082. S2CID 229178658.