Immunogenicity and Cross-Protection Efficacy of a Genotype F-Derived Attenuated Virus Vaccine Candidate against Mumps Virus in Mice

Abstract

Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain Jeryl Lynn (JL) is declining as genotype A is no longer predominant; therefore, a new vaccine strain and booster vaccine are required. We generated a cell culture-adapted MuV genotype F called F30 and evaluated its immunogenicity and cross-protective activity against diverse genotypes. F30 genome nucleotide sequence determination revealed changes in the NP, L, SH, and HN genes, leading to five amino acid changes compared to a minimally passaged stock (F10). F30 showed delayed growth, smaller plaque size in Vero cells, and lower neurotoxicity in neonatal mice than F10. Furthermore, F30 was immunogenic to other genotypes, including the JL vaccine strain, with higher efficacy than that of JL for homologous and heterologous immunization. Further, F30 exhibited cross-protective immunity against MuV genotypes F and G in Ifnar−/− mice after a third immunization with F30 following two doses of JL. Our data suggest that the live-attenuated virus F30 could be an effective booster vaccine to control breakthrough infections and mumps epidemics.