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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Hemorrhagic Fever, Ebola*/prevention & control ; Hemorrhagic Fever, Ebola*/immunology ; Ebola Vaccines*/immunology ; Ebola Vaccines*/administration & dosage ; Ebolavirus*/immunology ; Viral Envelope Proteins*/immunology ; Viral Envelope Proteins*/genetics ; Immunogenicity, Vaccine*; Animals ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Macaca fascicularis ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Disease Models, Animal ; Vaccination ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/administration & dosage ; Female ; Male ; Vaccine Efficacy

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 × 10 ⁸ to 1 × 10 ² 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.

PLoS One. 2009;4(5):e5547. (PMID: 19440245)
PLoS One. 2019 Apr 18;14(4):e0215457. (PMID: 30998735)
Viruses. 2015 Dec 19;7(12):6739-54. (PMID: 26703716)
Viruses. 2018 Dec 02;10(12):. (PMID: 30513823)
N Engl J Med. 2017 Oct 12;377(15):1438-1447. (PMID: 29020589)
J Virol. 2004 Jan;78(2):958-67. (PMID: 14694127)
Vaccines (Basel). 2022 Sep 01;10(9):. (PMID: 36146524)
J Infect Dis. 2019 Aug 30;220(7):1127-1135. (PMID: 31505665)
Vaccine X. 2019 Jan 29;1:100009. (PMID: 31384731)
J Infect Dis. 2017 Jun 15;215(12):1789-1798. (PMID: 28549145)
PLoS One. 2016 Mar 22;11(3):e0150919. (PMID: 27002733)
J Infect Dis. 2018 May 18;217(suppl_1):S6-S15. (PMID: 29788345)
N Engl J Med. 2014 Nov 27;371(22):2092-100. (PMID: 25353969)
PLoS Pathog. 2008 Nov;4(11):e1000225. (PMID: 19043556)
Science. 2015 Aug 14;349(6249):739-42. (PMID: 26249231)
PLoS One. 2020 Oct 29;15(10):e0241016. (PMID: 33119638)
Lancet. 2017 Feb 4;389(10068):505-518. (PMID: 28017403)
Emerg Infect Dis. 2019 Feb;25(2):249-255. (PMID: 30500321)
Vaccine. 2020 Jun 26;38(31):4885-4891. (PMID: 32499064)
Lancet Infect Dis. 2018 Jul;18(7):738-748. (PMID: 29627147)
J Infect Dis. 2015 Oct 1;212 Suppl 2:S91-7. (PMID: 26063223)
N Engl J Med. 2016 Apr 28;374(17):1647-60. (PMID: 25830326)
Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1893-8. (PMID: 23319647)
J Virol. 2009 Jul;83(14):7296-304. (PMID: 19386702)
Cell Rep. 2023 Apr 25;42(4):112402. (PMID: 37061918)
PLoS Med. 2021 Feb 10;18(2):e1003273. (PMID: 33566817)
PLoS Med. 2017 Oct 6;14(10):e1002402. (PMID: 28985239)
Nat Rev Dis Primers. 2020 Feb 20;6(1):13. (PMID: 32080199)
EBioMedicine. 2017 May;19:107-118. (PMID: 28434944)
N Engl J Med. 2019 Dec 12;381(24):2293-2303. (PMID: 31774950)
N Engl J Med. 2017 Oct 12;377(15):1428-1437. (PMID: 26465681)
MMWR Morb Mortal Wkly Rep. 2024 Apr 25;73(16):360-364. (PMID: 38662631)
EBioMedicine. 2019 Nov;49:223-231. (PMID: 31631035)
N Engl J Med. 2015 Jun 18;372(25):2423-7. (PMID: 25950269)
N Engl J Med. 2022 Dec 29;387(26):2411-2424. (PMID: 36516078)
Lancet Microbe. 2021 Feb;2(2):e70-e78. (PMID: 35544244)
Viruses. 2016 Apr 21;8(4):113. (PMID: 27110807)
Lancet Infect Dis. 2017 Aug;17(8):854-866. (PMID: 28606591)
Viruses. 2020 Jan 13;12(1):. (PMID: 31941095)
CMAJ. 2017 Jun 19;189(24):E819-E827. (PMID: 28630358)
Lancet Infect Dis. 2015 Oct;15(10):1156-1166. (PMID: 26248510)
Med Mal Infect. 2014 Sep;44(9):412-6. (PMID: 25193630)
Nat Med. 2005 Jul;11(7):786-90. (PMID: 15937495)
N Engl J Med. 2017 Jan 26;376(4):330-341. (PMID: 25830322)
Clin Microbiol Infect. 2023 Dec;29(12):1587-1594. (PMID: 37661067)

N/A U.S Department of Health and Human Services (HHS); N/A Administration for Strategic Preparedness and Response (ASPR); HDTRA1-15-C-0058 Defense Threat Reduction Agency; HHSO100201700012C Biomedical Advanced Research and Development Authority (BARDA); N/A Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

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

0 (Ebola Vaccines)
0 (Antibodies, Viral)
0 (Antibodies, Neutralizing)
0 (Viral Envelope Proteins)
0 (Vaccines, Synthetic)

Date Created: 20250327 Date Completed: 20250515 Latest Revision: 20250515

20250515

PMC11945660

10.3390/v17030341

40143273