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 7

Transcriptional responses in AGMs after challenge with NiVB.

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Transcriptional responses in AGMs after challenge with NiVB. (A) Princip...
(A) Principal component analysis based on DPI (0, 4, 7, 10/terminal time points) and each group: prime only (rVSV-ΔG-NiVBG; n = 6; yellow), prime + boost (rVSV-ΔG-NiVBG; n = 5; maroon), vector control prime (rVSV-ΔG-EBOV-GP; n = 3; purple), and vector control prime + boost (rVSV-ΔG-EBOV-GP; n = 3; lavender). (B) Overall expression changes for each group at late disease (orange denotes upregulated transcripts; blue denotes downregulated transcripts; black denotes no expression change). (C and D) Heatmaps depicting the topmost downregulated (C) and upregulated (D) transcripts in specifically versus nonspecifically prime-only vaccinated subjects at late disease (Benjamini-Hochberg–adjusted P value < 0.05). A comparison of prime versus boosted subjects was also performed. Dots indicate transcripts mapping to interferon signaling (brown) and adaptive immunity (green) nSolver gene sets. In the heatmaps, red denotes upregulated transcripts, blue denotes downregulated transcripts, and white denotes no expression change. (E) Trend plot depicting overall nSolver-derived cell-type quantities in control and vaccinated (fatal or survivor) cohorts. (F) Pathway enrichment of differentially expressed transcripts (Benjamini-Hochberg–adjusted P value < 0.05) in specifically vaccinated subjects at late disease. Displayed are the mean −log10(P values). A Benjamini-Hochberg test was used to derive adjusted P values. PC1, principal component 1; PC2, principal component 2.