Immunogenicity of Mumps Virus Genotype G Vaccine Candidates in Jeryl Lynn-Immunized Mice
Kelsey Briggs1, Cara Kirby1, Ashley C Beavis1
1Department of Infectious Diseases, University of Georgiagrid.213876.9 College of Veterinary Medicine, Athens, Georgia, USA.
Abstract:
Mumps virus (MuV) causes a highly contagious human disease characterized by the enlargement of the parotid glands. In severe cases, mumps can lead to neurological complications such as aseptic meningitis and encephalitis. Vaccination with the attenuated Jeryl Lynn (JL) MuV vaccine has dramatically reduced the incidence of MuV infection. Recently, large outbreaks have occurred in vaccinated populations. The vaccine strain JL was generated from genotype A, while most current circulating strains belong to genotype G. In this study, we examined the immunogenicity and longevity of genotype G-based vaccines. We found that our recombinant genotype G-based vaccines provide robust neutralizing titers toward genotype G for up to 1 year in mice. In addition, we demonstrated that a third dose of a genotype G-based vaccine following two doses of JL immunization significantly increases neutralizing titers toward the genotype G strain. Our data suggest that after two doses of JL vaccination, which most people have received, a third dose of a genotype G-based vaccine can generate immunity against a genotype G strain. IMPORTANCE At present, most individuals have received two doses of the measles, mumps, and rubella (MMR) vaccine, which contains genotype A mumps vaccine. One hurdle in developing a new mumps vaccine against circulating genotype G virus is whether the new genotype G vaccine can generate immunity in humans that are immunized against genotype A virus. This work demonstrates that a novel genotype G-based vaccine can be effective in animals which received two doses of genotype A-based vaccine, suggesting that the lead genotype G vaccine may induce anti-G immunity in humans who have received two doses of the current vaccine, providing support for testing this vaccine in humans.
Insights
New genotype G mumps vaccines show promise for boosting immunity in individuals previously vaccinated with genotype A vaccines. A third dose of the genotype G vaccine significantly increases neutralizing titers against circulating mumps strains.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Mumps virus (MuV) causes contagious parotid gland enlargement and can lead to severe neurological complications.
- The current measles, mumps, and rubella (MMR) vaccine uses the Jeryl Lynn (JL) strain, derived from genotype A.
- Recent mumps outbreaks in vaccinated populations highlight the need for vaccines effective against currently circulating strains, primarily genotype G.
Purpose of the Study:
- To evaluate the immunogenicity and longevity of novel genotype G-based mumps vaccines.
- To determine if genotype G vaccines can elicit protective immunity in individuals previously immunized with genotype A vaccines.
Main Methods:
- Development of recombinant genotype G-based mumps vaccines.
- Assessment of neutralizing antibody titers against genotype G strains in mice over time.
- Evaluation of booster immunizations with genotype G vaccines following prior JL (genotype A) vaccination in animal models.
Main Results:
- Recombinant genotype G-based vaccines induced robust neutralizing titers against genotype G strains for up to one year in mice.
- A third dose of the genotype G vaccine significantly enhanced neutralizing titers against genotype G strains after two doses of JL (genotype A) vaccine.
- These findings suggest potential cross-protection or enhanced immunity in individuals with prior genotype A vaccination.
Conclusions:
- Genotype G-based mumps vaccines demonstrate promising immunogenicity and longevity in preclinical studies.
- A genotype G-based vaccine booster dose can significantly increase neutralizing antibody titers in a genotype A-primed model.
- These results support the potential efficacy of genotype G-based vaccines in populations vaccinated with current genotype A mumps vaccines, warranting human clinical trials.


