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. 2025 Feb 28;17(3):341.
doi: 10.3390/v17030341.

rVSVΔG-ZEBOV-GP Vaccine Is Highly Immunogenic and Efficacious Across a Wide Dose Range in a Nonhuman Primate EBOV Challenge Model

Amy C Shurtleff  1 , John C Trefry  1 , Sheri Dubey  2 , Melek M E Sunay  1 , Kenneth Liu  2 , Ziqiang Chen  2 , Michael Eichberg  2 , Peter M Silvera  1 , Steve A Kwilas  1 , Jay W Hooper  1 , Shannon Martin  1 , Jakub K Simon  2 , Beth-Ann G Coller  2 , Thomas P Monath  3
Affiliations

rVSVΔG-ZEBOV-GP Vaccine Is Highly Immunogenic and Efficacious Across a Wide Dose Range in a Nonhuman Primate EBOV Challenge Model

Amy C Shurtleff et al. Viruses. .

Abstract

The recombinant vesicular stomatitis virus-Zaire Ebolavirus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP) was highly effective against Ebola virus disease in a ring vaccination trial conducted during the 2014-2016 outbreak in Guinea and is licensed by regulatory agencies including US FDA, EMA, and prequalified by WHO. Vaccination studies in a nonhuman primate (NHP) model guided initial dose selection for clinical trial evaluation. We summarize two dose-ranging studies with the clinical-grade rVSVΔG-ZEBOV-GP vaccine candidate to assess the impact of dose level on immune responses and efficacy in an NHP Ebola virus (EBOV) challenge model. Forty-six cynomolgus macaques were vaccinated with a wide range of rVSVΔG-ZEBOV-GP doses and challenged 42 days later intramuscularly with 1000 pfu EBOV. Vaccination with rVSVΔG-ZEBOV-GP induced relatively high levels of EBOV-specific IgG and neutralizing antibodies, measured using the same validated assays as used in rVSVΔG-ZEBOV-GP clinical trials. Similar responses were observed across dose groups from 1 × 108 to 1 × 102 pfu. A single vaccination conferred 98% protection from lethal intramuscular EBOV challenge across all dose groups. These results demonstrate that robust antibody titers are induced in NHPs across a wide range of rVSVΔG-ZEBOV-GP vaccine doses, correlating with high levels of protection against death from EBOV challenge.

Keywords: ERVEBO; Ebolavirus; nonhuman primates; vaccine; vesicular stomatitis virus.

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Conflict of interest statement

A.C.S., J.C.T., M.M.E.S., P.M.S., J.W.H., S.M. and S.A.K. declare no conflicts of interest. S.D., K.L., M.E., Z.C., are employees of Merck Sharp & Dohme L.L.C., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. J.K.S. and B.-A.G.C. were employees at the time of this study of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, at the time of this study, and may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. T.P.M. was employee of NewLink Genetics Corp.

Figures

Figure 1
Figure 1
Antibody responses in nonhuman primates after single intramuscular administration of various doses of rVSVΔG-ZEBOV-GP determined using validated assays. Ebolavirus-glycoprotein (EBOV-GP)-specific immunoglobulin G antibody titers in (A) Study 1 and (B) Study 2. 60% plaque-reduction neutralization test (PRNT60) titers in (C) Study 1 and (D) Study 2. Three experimental groups (eight monkeys per group) in Study 1 received 1 × 108, 2 × 107, or 3 × 106 plaque-forming unit (pfu) intramuscular (IM) doses of rVSVΔG-ZEBOV-GP. Five experimental groups (four or five monkeys per group) in Study 2 received 3 × 106, 3 × 105, 3 × 104, 3 × 103, or 3 × 102 pfu IM doses of rVSVΔG-ZEBOV-GP. Antibody titers are presented as geometric means. ELISA, enzyme-linked immunosorbent assay; SD, standard deviation.
Figure 2
Figure 2
rVSVΔG-ZEBOV-GP vaccine viremia in Study 2. Five experimental groups (four or five monkeys per group) in Study 2 received 3 × 106, 3 × 105, 3 × 104, 3 × 103, or 3 × 102 plaque-forming unit (pfu) intramuscular (IM) doses of rVSVΔG-ZEBOV-GP. LLOD, lower limit of detection; PCR, polymerase chain reaction; SD, standard deviation.
Figure 3
Figure 3
Kaplan–Meier survival curve for Ebola virus-challenged nonhuman primates. (A) Study 1: Includes three experimental groups that received 1 × 108 (n = 8), 2 × 107 (n = 7), or 3 × 106 (n = 8) plaque-forming unit (pfu) intramuscular (IM) doses of rVSVΔG-ZEBOV-GP, and one unvaccinated naive control group (n = 3). One female animal in the 2 × 107 pfu group was humanely euthanized during the vaccination phase and prior to the challenge dose due to gastric bloat and was not included in the time to death analysis for Ebola virus challenge. (B) Study 2: Includes five experimental groups that received 3 × 106 (n = 4), 3 × 105 (n = 4), 3 × 104 (n = 4), 3 × 103 (n = 5), or 3 × 102 (n = 5) pfu IM doses of rVSVΔG-ZEBOV-GP, and one unvaccinated naive control group (n = 2).
Figure 4
Figure 4
Viral load in nonhuman primates after Ebola virus challenge. (A) Study 1: Includes three experimental groups that received 1 × 108 (n = 8), 2 × 107 (n = 7), or 3 × 106 (n = 8) plaque-forming unit (pfu) intramuscular (IM) doses of rVSVΔG-ZEBOV-GP, and one unvaccinated naive control group (n = 3). One female animal in the 2 × 107 pfu group was humanely euthanized during the vaccination phase and prior to the challenge dose due to gastric bloat and was not included. (B) Study 2: Includes five experimental groups that received 3 × 106 (n = 4), 3 × 105 (n = 4), 3 × 104 (n = 4), 3 × 103 (n = 5), 3 × 102 (n = 5) pfu IM doses of rVSVΔG-ZEBOV-GP, and one unvaccinated naive control group (n = 2). The upper dotted line represents the lower limit of quantitation (156.25 copies/mL) and the lower dotted line represents the lower limit of detection (62.5 copies/mL). * indicates the 8 animals that were chosen for PsVNA neutralization assay.
Figure 4
Figure 4
Viral load in nonhuman primates after Ebola virus challenge. (A) Study 1: Includes three experimental groups that received 1 × 108 (n = 8), 2 × 107 (n = 7), or 3 × 106 (n = 8) plaque-forming unit (pfu) intramuscular (IM) doses of rVSVΔG-ZEBOV-GP, and one unvaccinated naive control group (n = 3). One female animal in the 2 × 107 pfu group was humanely euthanized during the vaccination phase and prior to the challenge dose due to gastric bloat and was not included. (B) Study 2: Includes five experimental groups that received 3 × 106 (n = 4), 3 × 105 (n = 4), 3 × 104 (n = 4), 3 × 103 (n = 5), 3 × 102 (n = 5) pfu IM doses of rVSVΔG-ZEBOV-GP, and one unvaccinated naive control group (n = 2). The upper dotted line represents the lower limit of quantitation (156.25 copies/mL) and the lower dotted line represents the lower limit of detection (62.5 copies/mL). * indicates the 8 animals that were chosen for PsVNA neutralization assay.
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