OPINION

Glycoprotein GP as a basis for the universal vaccine against Ebola virus disease

Dolzhikova IV, Tukhvatulin AI, Gromova AS, Grousova DM, Tukhvatulina NM, Tokarskaya EA, Logunov DYu, Naroditskiy BS, Gintsburg AL
About authors

Gamaleya National Research Center for Epidemiology and Microbiology, Moscow, Russia

Correspondence should be addressed: Inna V. Dolzhikova
Gamalei 18, Moscow, 123098; moc.liamg@avokihzlod.i

About paper

Author contribution: Dolzhikova IV, Tukhvatulin AI and Logunov DY conceived and planned the study, analyzed the literature, collected, analyzed and interpreted the data; Gromova AS, Grousova DM, Tukhvatulina NM, and Tokarskaya EA helped to collect and analyze the data; Naroditskiy BS and Gintsburg AL contributed to data interpretation; Dolzhikova IV wrote this manuscript.

Received: 2018-12-06 Accepted: 2019-02-20 Published online: 2019-03-03
|
  1. Beer B, Kurth R, Bukreyev A. Characteristics of Filoviridae: Marburg and Ebola viruses. Naturwissenschaften. 1999; 86 (1): 8–17.
  2. Kuhn JH, Becker S, Ebihara H, Geisbert TW, Johnson KM, Kawaoka Y, et al. Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations. Archives of Virology. 2010; 155 (12): 2083–103.
  3. Goldstein T, Anthony SJ, Gbakima A, Bird BH, Bangura J, Tremeau-Bravard A, et al. The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses. Nature Microbiology. 2018; 3 (10): 1084–89.
  4. CDC. Cases and Outbreaks of EVD by Year [updated 2018 Nov 9; cited 2018 Nov 12]. Available from: https://www.cdc.gov/vhf/ ebola/history/chronology.html.
  5. Lévy Y, Lane C, Piot P, Beavogui AH, Kieh M, Leigh B, et al. Prevention of Ebola virus disease through vaccination: where we are in 2018. Lancet. 2018; 392 (10149): 787–90.
  6. Bharat TA, Noda T, Riches JD, Kraehling V, Kolesnikova L, Becker S, et al. Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. Proc Natl Acad Sci USA. 2012; 109 (11): 4275–80.
  7. Volchkov VE, Becker S, Volchkova VA, Ternovoj VA, Kotov AN, Netesov SV, et al. GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology. 1995; 214 (2): 421–30.
  8. Cook JD, Lee JE. The Secret Life of Viral Entry Glycoproteins: Moonlighting in Immune Evasion. PLoS Pathog. 2013; 9 (5): e1003258.
  9. He J, Melnik LI, Komin A, Wiedman G, Fuselier T, Morris CF, et al. Ebola Virus Delta Peptide is a Viroporin. J Virol. 2017; 91 (16): e00438–17.
  10. Lee JE, Saphire EO. Ebolavirus glycoprotein structure and mechanism of entry. Future virology. 2009; 4 (6): 621–35.
  11. Wang H, Shi Y, Song J, Qi J, Lu G, Yan J, et al. Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1. Cell. 2016; 164 (1–2): 258–68.
  12. Sanchez A, Yang ZY, Xu L, Nabel GJ, Crews T, Peters CJ. Biochemical Analysis of the Secreted and Virion Glycoproteins of Ebola Virus. J Virol. 1998; 72 (8): 6442–47.
  13. Dolnik O, Volchkova V, Garten W, Carbonnelle C, Becker S, Kahnt J, et al. Ectodomain shedding of the glycoprotein GP of Ebola virus. EMBO J. 2004; 23 (10): 2175–84.
  14. Ito H, Watanabe S, Takada A, Kawaoka Y. Ebola Virus Glycoprotein: Proteolytic Processing, Acylation, Cell Tropism, and Detection of Neutralizing Antibodies. J Virol. 2001; 75 (3): 1576–80.
  15. Kuzmina NA, Younan P, Gilchuk P, Santos RI, Flyak AI, Ilinykh PA, et al. Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors. Cell Rep. 2018; 24 (7): 1802–15.
  16. Sullivan NJ, Geisbert TW, Geisbert JB, Shedlock DJ, Xu L, Lamoreaux L, et al. Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs. PLoS Med. 2006; 3 (6): e177.
  17. Li W, Ye L, Carrion R, Nunneley J, Staples H, Ticer A, et al. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice. J Infect Dis. 2015; 212 (Suppl 2): S398–403.
  18. Saphire EO, Schendel SL, Fusco ML, Gangavarapu K, Gunn BM, Wec AZ, et al. Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection. Cell. 2018; 174 (4): 938–52.
  19. Wec AZ, Herbert AS, Murin CD, Nyakatura EK, Abelson DM, Fels JM, et al. Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses. Cell. 2017; 169 (5): 878–90.
  20. Gilchuk P, Kuzmina N, Ilinykh PA, Huang K, Gunn BM, Bryan A, et al. Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein. Immunity. 2018; 49 (2): 363–74.
  21. Flyak AI, Kuzmina N, Murin CD, Bryan C, Davidson E, Gilchuk P, et al. Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2-MPER region. Nat Microbiol. 2018; 3 (6): 670–77.
  22. Sakabe S, Sullivan BM, Hartnett JN, Robles-Sikisaka R, Gangavarapu K, Cubitt B, et al. Analysis of CD8+ T cell response during the 2013–2016 Ebola epidemic in West Africa. Proc Natl Acad Sci USA. 2018; 115 (32): E7578–E7586.
  23. Lévy Y, Lane C, Piot P, Beavogui AH, Kieh M, Leigh B, et al. Prevention of Ebola virus disease through vaccination: where we are in 2018. Lancet. 2018; 392 (10149): 787–90.
  24. Dolzhikova IV, Tokarskaya EA, Dzharullaeva AS, Tukhvatulin AI, Shcheblyakov DV, Voronina OL, et al. Virus-Vectored Ebola Vaccines. Acta Naturae. 2017; 9 (3): 4–11.
  25. Marzi A, Robertson SJ, Haddock E, Feldmann F, Hanley PW, Scott DP, et al. EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Science. 2015; 349 (6249): 739–42.
  26. Macneil A, Reed Z, Rollin PE. Serologic cross-reactivity of human IgM and IgG antibodies to five species of Ebola virus. PLoS Negl Trop Dis. 2011; 5 (6): 1175.
  27. Natesan M, Jensen SM, Keasey SL, Kamata T, Kuehne AI, Stonier SW, et al. Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses. Clin Vaccine Immunol. 2016; (23): 717–24.
  28. Hensley LE, Mulangu S, Asiedu C, Johnson J, Honko AN, Stanley D, et al. Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus Species. PLoS Pathog. 2010; 6 (5): e1000904.
  29. Mire CE, Geisbert JB, Marzi A, Agans KN, Feldmann H, Geisbert TW. Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus. PLoS Negl Trop Dis. 2013; (7): e2600.
  30. Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, et al. Vesicular stomatitis virus-based Ebola vaccines with improved cross-protective efficacy. J Infect Dis. 2011; 204 (Suppl 3): S1066–74.
  31. Hatcher EL, Zhdanov SA, Bao Y, Blinkova O, Nawrocki EP, Ostapchuck Y, et al. Virus Variation Resource — improved response to emergent viral outbreaks. Nucleic Acids Res. 2016; 45 (D1): 482–90.
  32. T Cell Epitope Prediction Tools [cited 2018 Nov 12]. Available from: http://tools.iedb.org/main/tcell/.
  33. Ilinykh PA, Santos RI, Gunn BM, Kuzmina NA, Shen X, Huang K, et al. Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap. PLoS Pathog. 2018; 14 (8): e1007204.
  34. Audet J, Wong G, Wang H, Lu G, Gao GF, Kobinger G, et al. Molecular characterization of the monoclonal antibodies composing ZMAb: a protective cocktail against Ebola virus. Sci Rep. 2014; (4): 6881.
  35. Murin CD, Fusco ML, Bornholdt ZA, Qiu X, Olinger GG, Zeitlin L, et al. Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl Acad Sci USA. 2014; 111 (48): 17182–7.
  36. Ponomarenko J, Vaughan K, Sette A, Maurer-Stroh S. Conservancy of mAb Epitopes in Ebolavirus Glycoproteins of Previous and 2014 Outbreaks. PLoS Curr. 2014; (6).
  37. Zhao X, Howell KA, He S, Brannan JM, Wec AZ, Davidson E, et al. Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability. Cell. 2017; 169 (5): 891–904.
  38. Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, et al. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 2016; 351 (6279): 1343–6.