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Published on: February 10, 2022
Single-dose live-attenuated Nipah virus vaccines confer complete protection by eliciting antibodies directed against
Blair L DeBuysscher1, Dana Scott2, Andrea Marzi3
1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA; Division of Biological Sciences, University of Montana, Missoula, MT, USA.
Background:
Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks.
Methods:
In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies.
Results:
Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection.
Conclusions:
The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management.
Insights
New Nipah virus (NiV) vaccines using recombinant vesicular stomatitis virus (rVSV) vectors expressing NiV G or F proteins offer complete protection in hamsters. These emergency vaccines show promise for NiV outbreak control.
Area of Science:
- Virology
- Vaccinology
- Infectious Diseases
Background:
- Nipah virus (NiV) is a zoonotic pathogen causing severe respiratory illness and encephalitis.
- NiV outbreaks have occurred frequently since 2001, posing a significant public health threat due to high fatality and human-to-human transmission.
- There is an urgent need for effective intervention options, including vaccines, for NiV outbreak management.
Purpose of the Study:
- To develop a fast-acting, single-dose Nipah virus vaccine.
- To evaluate the potential for a ring vaccination approach during NiV outbreaks.
Main Methods:
- Designed live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV).
- Expressed NiV glycoproteins (G or F) or nucleoprotein (N) using rVSV vectors.
- Evaluated protective efficacy in Syrian hamsters, assessing humoral immune responses via ELISA and neutralization assays, and performing serum transfer studies.
Main Results:
- Single-dose rVSV vaccines expressing NiV G or F proteins induced strong humoral immune responses with neutralizing activity.
- Animals vaccinated with rVSV-NiV G or F were completely protected from lethal NiV infection.
- rVSV-NiV N vaccination provided partial protection, which was not antibody-dependent, suggesting a role for cellular immunity.
Conclusions:
- rVSV vectors expressing Nipah virus G or F glycoproteins are strong candidates for emergency Nipah virus vaccines.
- These vaccines could be crucial for managing NiV outbreaks effectively.
- The findings support the development of rapid-response vaccination strategies for emerging infectious diseases.
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