Mumps virus (MuV), a paramyxovirus, causes acute inflammatory infections in humans involving most organ systems. Mumps virus infection was the most common cause of viral meningitis and encephalitis before mass immunization with the mumps virus vaccine. Advisory Committee on Immunization Practices (ACIP) recommended a single dose immunization of MuV vaccine in 1977 and in 1989 ACIP recommended to increase MuV vaccine to two doses. Even with widespread vaccination programs in place, mumps outbreaks continue to occur. The largest MuV outbreak in the US after implementation of two-dose MuV vaccination program occurred in 2006. It is considered the first failure of two-dose MuV vaccination. In 2010, a large MuV outbreak occurred in NY/NJ area. While definitive causes for the outbreaks are not known, possible reasons (not mutually exclusive) for these outbreaks include (1) waning immunity and (2) vaccine failure due to emergence of a new mumps virus strain. The fact that outbreaks had occurred in populations with over 95% coverage of two-dose MuV vaccine strongly suggests that the current vaccine is not effective. The current vaccine is based on genotype A while outbreaks were caused by genotype G MuV. All these possible causes indicate a need for a new vaccine that is effective against current outbreak strain of mumps virus. Long-term goal of this proposal is to develop a new mumps virus vaccine with long-lasting immunity. We hypothesize that MuV mutants generated using reverse genetics system are good vaccine candidates. We propose to develop a novel mumps virus vaccine by attenuating virus through introducing mutations at desirable locations within the genome and to test immunogenicity of vaccine candidates in mice and ferrets.

Public Health Relevance

Current mumps virus vaccine (JL strain) based on genotype A has been used for over 40 years. Recently, large outbreaks in vaccinated populations have occurred at increasing frequency. The outbreaks of mumps virus (genotype G) infection in vaccinated populations underscore the urgency and importance of developing a new and effective vaccine against mumps virus (genotype G) that caused current outbreaks.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI097368-03
Application #
8650782
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Cassetti, Cristina
Project Start
2012-05-10
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Georgia
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
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