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Handling of the Cotton Rat in Studies for the Pre-clinical Evaluation of Oncolytic Viruses
Published on: November 24, 2014
Evaluation of immunogenicity of mumps vaccine strains in cotton rat (Sigmodon hispidus) model
Takashi Ito1, Yoshiaki Yamaji2, Akihito Sawada2
1Kitasato University, Ōmura Satoshi Memorial Institute, Laboratory of Virus Infection, Japan; Kitasato University, School of Medicine, Department of Pediatrics, Japan.
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.
Insights
The RIT 4385 mumps vaccine showed lower viral genome distribution but comparable T cell induction and protection versus the Hoshino strain in cotton rats. Cotton rats are a useful model for mumps vaccine development.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- The RIT 4385 strain, derived from Jeryl Lynn, is a component of the measles, mumps, and rubella (MMR) vaccine used globally.
- The Hoshino strain is the domestic mumps vaccine used in Japan.
- Evaluating vaccine immunogenicity and efficacy in animal models is crucial for public health.
Purpose of the Study:
- To compare the immunogenicity and protective efficacy of the RIT 4385 mumps vaccine against the Hoshino strain in a cotton rat model.
- To investigate the systemic distribution of the mumps virus (MuV) genome and host immune responses following vaccination.
Main Methods:
- Cotton rats were inoculated with RIT 4385 or Hoshino strain mumps vaccines.
- Mumps virus genome distribution was assessed in various tissues at 1, 2, and 3 weeks post-inoculation.
- Cytokine mRNA production (IFN-γ), CD8+/IFN-γ+ T cell responses, and serum neutralizing antibodies (Nab) were measured.
- Animals were re-immunized and subsequently challenged with a wild-type mumps strain.
Main Results:
- The MuV genome was detected in tissues for up to 2 weeks, with higher detection rates for the Hoshino strain compared to RIT 4385.
- IFN-γ mRNA and CD8+/IFN-γ+ T cells were induced by both vaccine strains.
- Both vaccines elicited neutralizing antibodies against wild-type MuV (genotype G), with RIT 4385 showing a lower initial response but similar levels after secondary immunization.
- Protective effects against wild-type mumps challenge were observed in both vaccine groups.
Conclusions:
- RIT 4385 demonstrates gradual growth with reduced MuV genome distribution compared to the Hoshino strain.
- Despite differences in viral distribution, both vaccines induced comparable CD8+/IFN-γ+ T cell responses and protection.
- The cotton rat model is validated as a suitable platform for evaluating mumps vaccine development and efficacy.
