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 4

Pathology of vaccinated and control NiVB-infected AGMs.

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Pathology of vaccinated and control NiVB-infected AGMs. Representative p...
Representative photomicrographs of immunohistochemistry (IHC) for anti-NiV antigen (brown) in lung (B and D), spleen (F and H), liver (J and L), kidney (N and P), and brain (R and T); and H&E staining of the lung (A and C), spleen (E and G), liver (I and K), kidney (M and O), and brain (Q and S). All photomicrographs were taken at ×20 magnification. Micrographs shown are from positive controls VC-P-3 (A, B, E, F, I, J, M, and N) and VC-P-2 (Q and R). (A) Loss of normal pulmonary alveolar architecture with inflamed and necrotic alveolar septa and flooding of alveolar spaces with fibrin, edema, and hemorrhage. (B) IHC-positive endothelium and mononuclear cells within the alveolar septa and alveolar macrophages. (E) Loss of splenic germinal center architecture with lymphocytolysis, syncytial cell formation, and hemorrhage. (F) IHC-positive mononuclear cells concentrated in the white pulp and scattered within the red pulp. (I) Sinusoidal leukocytosis. (J) IHC positivity of sinusoidal lining cells and Kupffer cells (black arrows). (M) Renal glomerular congestion. (N) Segmental IHC-positive glomerular endothelium and mononuclear cells (black arrow). (Q) Diffuse gliosis of the brainstem. (R) IHC-positive neuronal cells of the brainstem (black arrow). No appreciable immunolabeling or lesions were noted in the lung, spleen, liver, kidney, or brain of representative rVSV-ΔG-NiVBG–surviving AGM P-3 (C, D, G, H, K, L, O, P, S, and T).