2021 FDA Science Forum
A Mumps Virus Genotype G Vaccine Candidate Displays Enhanced Neutralization of Circulating Variants over the Current Genotype A Jeryl Lynn Vaccine
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Contributing OfficeCenter for Biologics Evaluation and Research
Abstract
Introduction
Despite widespread childhood mumps vaccination, outbreaks continue to occur, particularly among adults, which is believed to be due to a combination of waning immunity and antigenic drift. The currently approved mumps vaccine (Jeryl Lynn) developed in the 1960’s is a live, attenuated virus belonging to the genotype A group of mumps virus strains based on a genetic classification system. Genotype A strains have not been circulating since the 1980’s. While serum from Jeryl Lynn (JL) vaccinees can neutralize mumps viruses belonging to all other genotypes in vitro, the potency of sera against heterologous genotypes is greatly reduced. This has resulted in calls for development of new, more effective mumps vaccines better representative of circulating strains of the virus. To this end, we created an attenuated mumps vaccine candidate expressing the consensus viral fusion (F) and hemagglutinin (HN) protein sequences of the genotype G strains (circulating globally for over a decade) on the backbone the current Jeryl Lynn (JL) vaccine and named this vaccine candidate JL-G.
Methods
The immunogenicity of JL-G versus JL was assessed in rhesus macaques (n=5 per group) by testing serum collected at various times points following a second dose of each vaccine by plaque reduction neutralization assay against a panel of virus genotypes.
Results
The neutralizing geometric mean titers (GMT) of sera from the JL-G vaccinated animals against the JL-G virus was 18-fold higher as compared to sera from JL vaccinated animals. GMTs were also higher with JL-G sera when tested against JL and other genotypes (B, C, G, H, K, and N) as compared to JL sera. No fever or other adverse reaction was observed in any animal.
Conclusion
We successfully produced a mumps vaccine candidate that provided superior neutralization across all genotypes tested in this study when compared to the current JL vaccine. This enhanced ability to neutralize current circulating mumps strains may mitigate the effects of waning immunity in vaccinated individuals.
