A single-cycle, recombinant VSV platform Nipah vaccine cross-protects against Hendra virus in nonhuman primates
- 1Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, United States of America
- 2Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America
Abstract
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic paramyxoviruses that produce severe, often fatal disease in humans and animals. Zoonotic spillover of these henipaviruses from the Pteropid bat natural reservoir occurs near-annually in Southeast Asia and Oceania. Outbreaks of NiV disease frequently exceed case fatality rates of 75%, and person-to-person transmission makes controlling outbreaks in low-resource environments challenging. HeV is less transmissible between humans; however, the overall mortality rate is 57%. Approaches to human vaccine development have largely focused on NiV given the larger case burden, and immunogen selection has centered on display of the NiV attachment (G) or fusion (F) surface glycoproteins. However, experimental vaccines displaying these NiV antigens have failed to uniformly cross-protect against HeV disease in preclinical models. The HeV (G) antigen was shown to cross-protect against both HeV and NiV when delivered in a protein subunit form; however, attempts to utilize mRNA or canarypox vectors failed to achieve equivalent protection. We previously developed and evaluated a single-cycle recombinant vesicular stomatitis virus-vectored vaccine displaying the (G) glycoprotein of Nipah virus strain Bangladesh (NiV-B). This experimental vaccine (G*rVSV∆G-NiV-G) demonstrated ideal characteristics of rapid and durable protection against NiV-B challenge in nonhuman primates. In the present work, we show that the G*rVSV∆G-NiV-G vaccine cross-protects against lethal HeV challenge, with the protective response driven by a balance of both cell-mediated and humoral compartments. Author summary: Emerging viruses Nipah and Hendra were first identified as human pathogens in the 1990s and can cause severe, often fatal disease for which there are no approved medical countermeasures. Both viruses are found to naturally circulate in fruit bats, which can transmit the virus to amplifying hosts such as horses and pigs, presenting a risk to both human and veterinary health. Vaccine countermeasures to protect humans against either virus are not available. We previously showed that a single dose of a recombinant vesicular stomatitis virus (rVSV) vectored vaccine incorporating a Nipah glycoprotein antigen could rapidly protect animals from lethal Nipah disease. Hendra virus is closely related to Nipah, and an ideal vaccine countermeasure should offer protection against both pathogens. In the present work, we performed experiments to investigate whether a single dose of the rVSV Nipah vaccine could also protect against Hendra virus. We found that the rVSV Nipah vaccine protected nonhuman primates from lethal Hendra virus disease and that protection was likely due to a combined immune response involving both humoral and cellular components. Our study suggests that cross-protection against Hendra virus by vaccination with a Nipah antigen vaccine likely requires a T-cell response, which has previously not been described.
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BibTeX
@article{pigeaud2026singlecycle,
title = {{A single-cycle, recombinant VSV platform Nipah vaccine cross-protects against Hendra virus in nonhuman primates}},
author = {Declan D. Pigeaud and Viktoriya Borisevich and Jacquelyn Turcinovic and Krystle N. Agans and Daniel J. Deer and Mack B. Harrison and Rachel O’Toole and Natalie S. Dobias and Abhishek N. Prasad and Karla A. Fenton and Robert W. Cross and Thomas W. Geisbert},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014646},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014646},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A single-cycle, recombinant VSV platform Nipah vaccine cross-protects against Hendra virus in nonhuman primates
AU - Declan D. Pigeaud
AU - Viktoriya Borisevich
AU - Jacquelyn Turcinovic
AU - Krystle N. Agans
AU - Daniel J. Deer
AU - Mack B. Harrison
AU - Rachel O’Toole
AU - Natalie S. Dobias
AU - Abhishek N. Prasad
AU - Karla A. Fenton
AU - Robert W. Cross
AU - Thomas W. Geisbert
PY - 2026
DA - 2026/09/22
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014646
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014646
AB - Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic paramyxoviruses that produce severe, often fatal disease in humans and animals. Zoonotic spillover of these henipaviruses from the Pteropid bat natural reservoir occurs near-annually in Southeast Asia and Oceania. Outbreaks of NiV disease frequently exceed case fatality rates of 75%, and person-to-person transmission makes controlling outbreaks in low-resource environments challenging. HeV is less transmissible between humans; however, the overall mortality rate is 57%. Approaches to human vaccine development have largely focused on NiV given the larger case burden, and immunogen selection has centered on display of the NiV attachment (G) or fusion (F) surface glycoproteins. However, experimental vaccines displaying these NiV antigens have failed to uniformly cross-protect against HeV disease in preclinical models. The HeV (G) antigen was shown to cross-protect against both HeV and NiV when delivered in a protein subunit form; however, attempts to utilize mRNA or canarypox vectors failed to achieve equivalent protection. We previously developed and evaluated a single-cycle recombinant vesicular stomatitis virus-vectored vaccine displaying the (G) glycoprotein of Nipah virus strain Bangladesh (NiV-B). This experimental vaccine (G*rVSV∆G-NiV-G) demonstrated ideal characteristics of rapid and durable protection against NiV-B challenge in nonhuman primates. In the present work, we show that the G*rVSV∆G-NiV-G vaccine cross-protects against lethal HeV challenge, with the protective response driven by a balance of both cell-mediated and humoral compartments. Author summary: Emerging viruses Nipah and Hendra were first identified as human pathogens in the 1990s and can cause severe, often fatal disease for which there are no approved medical countermeasures. Both viruses are found to naturally circulate in fruit bats, which can transmit the virus to amplifying hosts such as horses and pigs, presenting a risk to both human and veterinary health. Vaccine countermeasures to protect humans against either virus are not available. We previously showed that a single dose of a recombinant vesicular stomatitis virus (rVSV) vectored vaccine incorporating a Nipah glycoprotein antigen could rapidly protect animals from lethal Nipah disease. Hendra virus is closely related to Nipah, and an ideal vaccine countermeasure should offer protection against both pathogens. In the present work, we performed experiments to investigate whether a single dose of the rVSV Nipah vaccine could also protect against Hendra virus. We found that the rVSV Nipah vaccine protected nonhuman primates from lethal Hendra virus disease and that protection was likely due to a combined immune response involving both humoral and cellular components. Our study suggests that cross-protection against Hendra virus by vaccination with a Nipah antigen vaccine likely requires a T-cell response, which has previously not been described.
SN - 1553-7374
ER -