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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
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Safety and Immunogenicity of a Stable, Cold-Adapted, Temperature-Sensitive/Conditional Lethal Enterovirus A71 in
Kaw Bing Chua1, Qimei Ng1, Tao Meng1
1Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore.
Viruses
|April 3, 2021
Summary
Researchers developed a stable, cold-adapted Enterovirus A71 (EV-A71) vaccine candidate. This temperature-sensitive virus showed genetic stability and induced a humoral immune response in monkeys, offering a promising avenue for hand, foot, and mouth disease (HFMD) prevention.
Area of Science:
- Virology
- Vaccinology
- Public Health
Background:
- Enterovirus A71 (EV-A71) and coxsackievirus A16 (CA16) are primary causes of hand, foot, and mouth disease (HFMD) in children.
- HFMD can lead to severe neurological complications, making vaccine development a global health priority, especially for developing nations.
Purpose of the Study:
- To generate a stable, cold-adapted, temperature-sensitive/conditional lethal mutant of EV-A71 for potential vaccine development.
- To assess the phenotypic and genetic stability of the engineered EV-A71 strain.
- To evaluate the safety and immunogenicity of the candidate vaccine in a non-human primate model.
Main Methods:
- Adaptive culturing of EV-A71 in Vero cells at progressively lower temperatures.
- Passaging the virus at 28°C and conducting temperature reversion studies at 37°C and 39.5°C.
- Administering the engineered EV-A71 to six monkeys and monitoring for clinical signs, performing postmortem analysis, and assessing viral RNA and antigen presence, alongside humoral immune response.
Main Results:
- A stable, cold-adapted, temperature-sensitive/conditional lethal EV-A71 strain was successfully generated.
- The engineered virus demonstrated phenotypic and genetic stability, with six unique mutations contributing to its characteristics.
- Monkeys inoculated with the candidate vaccine showed no significant clinical illness or gross pathology, with detectable EV-A71 RNA and viral antigen in specific tissues and serum, and a notable humoral immune response.
Conclusions:
- The developed stable, cold-adapted, temperature-sensitive EV-A71 is a promising candidate for a safe and effective HFMD vaccine.
- The genetic and phenotypic stability of the mutant virus supports its potential for further development.
- The observed safety and immunogenicity in monkeys provide a strong rationale for advancing this vaccine candidate towards human trials.
