A recombinant VSV-vectored vaccine rapidly protects nonhuman primates against lethal Nipah virus disease

• Published in: Proceedings of the National Academy of Sciences - PNAS 2022-03, Vol.119 (12), p.1-12
• Main Authors: Foster, Stephanie L., Woolsey, Courtney, Borisevich, Viktoriya, Agans, Krystle N., Prasad, Abhishek N., Deer, Daniel J., Geisbert, Joan B., Dobias, Natalie S., Fenton, Karla A., Cross, Robert W., Geisbert, Thomas W.
• Format: Article
• Language: English
• Subjects: Animal diseases; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral - immunology; Biological Sciences; Biomarkers; Cytotoxicity; Genetic Vectors; Glycoproteins; Henipavirus Infections - veterinary; Humoral immunity; Immunization; Interferon; Kaplan-Meier Estimate; Lethal dose; Lethality; Lymphocytes; Lymphocytes T; Monkeys; Monkeys & apes; Natural killer cells; Neutralization Tests; Nipah virus; Nipah Virus - immunology; Outcome Assessment, Health Care; Primate Diseases - diagnosis; Primate Diseases - mortality; Primate Diseases - prevention & control; Primate Diseases - virology; Severe acute respiratory syndrome coronavirus 2; Stomatitis; Transcription; Transcriptomics; Vaccination; Vaccines; Vaccines, Synthetic - immunology; Viral diseases; Viral Load; Viral Vaccines - immunology; Viruses; Zoonoses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2200065119

Nipah virus (NiV) is an emerging highly lethal zoonotic disease that, like SARS-CoV-2, can be transmitted via respiratory droplets. Single-injection vaccines that rapidly control NiV outbreaks are needed. To assess the ability of a vaccine to induce fast-acting protection, we immunized African green monkeys with a recombinant vesicular stomatitis virus (VSV) expressing the Bangladesh strain glycoprotein (NiVBG) of NiV (rVSV-ΔG-NiVBG). Monkeys were challenged 3 or 7 d later with a lethal dose of NiVB. All monkeys vaccinated with rVSV-ΔG-NiVBG 7 d prior to NiVB exposure were protected from lethal disease, while 67% of animals vaccinated 3 d before NiVB challenge survived. Vaccine protection correlated with natural killer cell and cytotoxic T cell transcriptional signatures, whereas lethality was linked to sustained interferon signaling. NiV G-specific antibodies in vaccinated survivors corroborated additional transcriptomic findings, supporting activation of humoral immunity. This study demonstrates that rVSV-based vaccines may have utility in rapidly protecting humans against NiV infection.