Evaluation of immunogenicity of mumps vaccine strains in cotton rat (Sigmodon hispidus) model.

OBJECTIVES

RIT 4385 (RIT) is cloned from the Jeryl Lynn mumps vaccine strain and is widely used in measles, mumps, and rubella combined vaccine (MMR) in many countries. Immunogenicity of RIT was investigated in cotton rats in comparison with domestic mumps vaccine (Hoshino strain) used in Japan.

METHODS

Systemic distribution of mumps virus (MuV) genome was investigated in kidney, salivary glands, pancreas, testis/ovary, and brain tissues obtained at 1, 2, and 3 weeks after inoculation. Cytokine mRNA production was investigated in comparison with inoculation with Mp/Tokyo.SIII-10/JPN.2001 (SIII-10, genotype L) and Mp/Takamatsu.N58/JPN.2001 (N58, genotypes G) strains. Spleen cells were stimulated with specific peptides to investigate the development of CD8+/IFN-γ+ T cells. Cotton rats were re-immunized 8 weeks after the first dose, and the development of serum neutralizing test antibodies (Nab) was examined. After the second dose, rats were challenged with wild strain (N-58, genotype G).

RESULTS

MuV genome was detected from tissues obtained at 1-2 weeks, with higher detection rate after inoculation with Hoshino than with RIT and decreased 3 weeks after inoculation. IFN-γ mRNA was detected in the salivary glands and in the testis/ovary 1 week after inoculation with RIT and Hoshino, respectively. CD8+/IFN-γ+ T cells were elevated 2 weeks after inoculation with both vaccine and wild strains. Nab against wild MuV (genotype G) increased after immunization with both Hoshino and RIT, being lower in rats immunized with RIT, but showed similar response at 8 weeks and after second doses. Protective effects were observed in both vaccine groups.

CONCLUSION

RIT grows gradually with lower MuV genome distribution, but there was no difference in the induction of CD8+/IFN-γ+ T cells and protection. Therefore, cotton rat is considered a useful animal model to evaluate the mump vaccine development.