Recombinant vesicular stomatitis virus–vectored vaccine induces long-lasting immunity against Nipah virus disease
Courtney Woolsey, … , Robert W. Cross, Thomas W. Geisbert
Courtney Woolsey, … , Robert W. Cross, Thomas W. Geisbert
Published November 29, 2022
Citation Information: J Clin Invest. 2023;133(3):e164946. https://doi.org/10.1172/JCI164946.
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Research Article Infectious disease

Recombinant vesicular stomatitis virus–vectored vaccine induces long-lasting immunity against Nipah virus disease

Abstract

The emergence of the novel henipavirus, Langya virus, received global attention after the virus sickened over three dozen people in China. There is heightened concern that henipaviruses, as respiratory pathogens, could spark another pandemic, most notably the deadly Nipah virus (NiV). NiV causes near-annual outbreaks in Bangladesh and India and induces a highly fatal respiratory disease and encephalitis in humans. No licensed countermeasures against this pathogen exist. An ideal NiV vaccine would confer both fast-acting and long-lived protection. Recently, we reported the generation of a recombinant vesicular stomatitis virus–based (rVSV-based) vaccine expressing the NiV glycoprotein (rVSV-ΔG-NiVBG) that protected 100% of nonhuman primates from NiV-associated lethality within a week. Here, to evaluate the durability of rVSV-ΔG-NiVBG, we vaccinated African green monkeys (AGMs) one year before challenge with an uniformly lethal dose of NiV. The rVSV-ΔG-NiVBG vaccine induced stable and robust humoral responses, whereas cellular responses were modest. All immunized AGMs (whether receiving a single dose or prime-boosted) survived with no detectable clinical signs or NiV replication. Transcriptomic analyses indicated that adaptive immune signatures correlated with vaccine-mediated protection. While vaccines for certain respiratory infections (e.g., COVID-19) have yet to provide durable protection, our results suggest that rVSV-ΔG-NiVBG elicits long-lasting immunity.

Authors

Courtney Woolsey, Viktoriya Borisevich, Alyssa C. Fears, Krystle N. Agans, Daniel J. Deer, Abhishek N. Prasad, Rachel O’Toole, Stephanie L. Foster, Natalie S. Dobias, Joan B. Geisbert, Karla A. Fenton, Robert W. Cross, Thomas W. Geisbert

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Figure 1

Vector and experimental design for the vaccination and challenge of AGMs.

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Vector and experimental design for the vaccination and challenge of AGMs...
(A) Schematic of pVSV-WT and pVSV-ΔG-NiVBG genomes. The NiVBG gene (green box) was cloned into the native VSV G gene site (yellow box) in a plasmid containing the entire rVSV genome and recovered in VSV G–complemented (pC-VSV-G) baby hamster kidney cells. Intergenic and 3′- or 5′-untranslated genomic regions are indicated by black lines. (B) Seventeen AGMs were randomized into 4 groups: prime only (n = 6), prime + boost (n = 5), vector control prime (n = 3), and vector control prime + boost (n = 3) groups. Each group received a 1 × 107 PFU i.m. dose of rVSV-ΔG-NiVBG vaccine or a nonspecific rVSV vector control expressing the Ebola virus glycoprotein (rVSV-ΔG-EBOV-GP). The prime + boost and vector control prime + boost groups received an additional dose at 56 days after vaccination. Blood samples were collected monthly at days 0, 10, 28, 56, 84, 112, 139, 164, 195, 221, 259, 294, 329, and 369 (0). AGMs were subsequently challenged 1 year later with an intranasal dose of 5 × 103 PFU of NiVB delivered by Mucosal Atomization Device. Post-exposure blood samples were collected at 4, 7, 10, 14, 21, 28, terminally, and/or 35 days. Blue pins indicate vaccination-phase sampling time points, whereas red lines denote challenge-phase sampling time points. N, nucleoprotein; P, phosphoprotein; M, matrix protein; G, glycoprotein; EBOV, Ebola virus.