Mapping the humoral immune response to the surface glycoproteins of the mumps virus

The National Institute of Allergy and Infectious Diseases awarded La Jolla Institute for Immunology $279,000 on May 15, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop panels of human monoclonal antibodies against mumps virus surface glycoproteins HN and F from vaccinated and convalescent individuals. The research aims to characterize the humoral immune response to mumps virus, identify which antibody epitope target sites confer broadest viral genotype recognition—particularly between vaccine-derived genotype A and circulating genotype G—and generate monoclonal antibodies suitable for post-exposure treatment development and vaccine booster design. The work addresses a gap in basic immunological knowledge: despite the MMR vaccine's use since 1971, human antibody responses to mumps virus remain uncharacterized and no structures of mumps-specific antibodies have been determined, yet mumps outbreaks continue among vaccinated populations. Performance occurs in La Jolla, California, with a period of performance through April 30, 2028.

Abstract

Mumps virus is one component of the MMR vaccine, which has been successful in the global effort against measles, mumps and rubella. However, of the three viruses, protection against mumps is the least effective. Cycles of mumps virus outbreaks continue to occur, especially among young adults and even in the vaccinated. 10% of patients in a recent SAN diego county outbreak were hospitalized. Breakthrough infections could be linked to sequence differences between the vaccine strain and the newly emerged mumps genotype g. Surprisingly, although we have had this vaccine since 1971, medical science still does not know what the human antibody response is against mumps virus, from either vaccination or natural infection. No human antibodies against mumps have been yet described, and no structures of any antibodies against mumps have yet been determined. Thus, we are lacking understanding of which antibodies and which epitope target sites on the surface proteins HN and f are most effective, and we are lacking the antibodies themselves which might be incorporated into post-exposure treatments. In this program, we will develop panels of human monoclonal antibodies against mumps HN and f from both vaccinated and convalescent individuals. Results obtained from this program will illuminate what humans target in their immune responses, and which target sites, or epitopes, lead to broadest viral genotype recognition, especially between vaccine-derived genotype a and currently circulating genotype g of the virus. The results of this program will also provide the essential mabs themselves from which we may develop post-exposure treatments and guide development of boosters.