Marburg vaccine

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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]

Contents

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

Related Research Articles

<span class="mw-page-title-main">Marburg virus disease</span> Human viral disease

Marburg virus disease (MVD), formerly Marburg hemorrhagic fever (MHF) is a viral hemorrhagic fever in human and non-human primates caused by either of the two Marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV). Its clinical symptoms are very similar to those of Ebola virus disease (EVD).

<i>Filoviridae</i> Family of viruses in the order Mononegavirales

Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.

<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.

<i>Marburgvirus</i> Genus of virus

The genus Marburgvirus is the taxonomic home of Marburg marburgvirus, whose members are the two known marburgviruses, Marburg virus (MARV) and Ravn virus (RAVV). Both viruses cause Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever. Both are select agents, World Health Organization Risk Group 4 Pathogens, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogens, Centers for Disease Control and Prevention Category A Bioterrorism Agents, and are listed as Biological Agents for Export Control by the Australia Group.

<span class="mw-page-title-main">Mayinga N'Seka</span> Congolese nurse who died from Ebola in 1976

Mayinga N'Seka was a nurse in Zaïre, now Democratic Republic of the Congo. She died from Ebola virus disease during the 1976 epidemic in Zaïre. She has been incorrectly identified as the index case by several sources, but a World Health Organization commission report on the outbreak lists a man from Yambuku, Mabalo Lokela, as the index case. Lokela, a 44-year-old who had been buying meat in Sudan, died on September 8, 1976, over a month before N'Seka.

<span class="mw-page-title-main">Lisa Hensley (microbiologist)</span> Microbiologist

Lisa Ellen Hensley is the associate director of science at the Office of the Chief Scientist, National Institute of Allergy and Infectious Disease Integrated Research Facility in Frederick, Maryland. She was previously a civilian microbiologist in the virology division of the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Hensley is one of the premier researchers of some of the world's most dangerous infections, including Ebola hemorrhagic fever, Lassa fever, the coronavirus diseases Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and smallpox. She has been involved in research uncovering critical mechanisms in the pathogenesis of hemorrhagic fever viruses, and has used those discoveries to develop candidate therapeutic drugs for their treatment.

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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">Marburg virus</span> Species of filamentous virus responsible for hemorrhagic fever

Marburg virus (MARV) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. It causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.

Ravn virus is a close relative of Marburg virus (MARV). RAVV causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever. RAVV is a Select agent, World Health Organization Risk Group 4 Pathogen, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, Centers for Disease Control and Prevention Category A Bioterrorism Agent, and listed as a Biological Agent for Export Control by the Australia Group.

<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.

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.

<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.

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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. 1 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. 1 2 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.
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  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. 1 2 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.PD-icon.svg 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.
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