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Virus strain specificity of challenge immunity to coronavirus
1Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
Abstract:
The resistance of immunized mice to challenge with the same or a different strain of mouse hepatitis virus (MHV) was examined as a model of challenge immunity to coronavirus infection. Genetically susceptible BALB/cByJ mice were given an intranasal immunizing infection of respiratory-type MHV-JHM, MHV-S, or enterotropic MHV-Y. Control mice were sham-immunized with sterile tissue culture fluid. Recovered mice were challenged intranasally with MHV-JHM, MHV-S or sterile tissue culture fluid at 30 days after immunization. Resistance to challenge inoculation was evaluated in groups of mice at 4 and 30 days after challenge. At 4 days, the prevalence of MHV lesions in nose and liver was tabulated and MHV titers in liver were determined. At 30 days, the prevalence of residual brainstem spongiform lesions was tabulated and serum antibody to MHV-JHM and MVH-S was quantified by enzyme immunoassay. Mice immunized with MHV-JHM or MHV-S resisted challenge with the MHV homotype, but MHV-S-immunized mice were fully susceptible to challenge with MVH-JHM. Mice immunized with enterotropic MHV-Y were only partially protected against challenge with antigenically related, but biologically different MHV-S. Serum antibody responses to MHV supported these observations. These data indicate that challenge immunity to coronaviruses is strong, but highly virus strain-specific.
Insights
Challenge immunity to mouse hepatitis virus (MHV) is robust but strain-specific. Immunized mice resisted homologous MHV strains but not heterologous ones, highlighting the importance of viral strain in coronavirus immunity.
Area of Science:
- Veterinary Virology
- Immunology
- Infectious Diseases
Background:
- Mouse hepatitis virus (MHV) is a significant cause of disease in laboratory mice.
- Understanding coronavirus challenge immunity is crucial for developing effective vaccines and treatments.
- BALB/cByJ mice, genetically susceptible to MHV, serve as a relevant model for studying host-pathogen interactions.
Purpose of the Study:
- To investigate the strain-specificity of challenge immunity following immunization with different MHV strains.
- To evaluate the protective efficacy of immunization against homologous and heterologous MHV challenge.
- To correlate serum antibody responses with observed resistance to MHV infection.
Main Methods:
- Intranasal immunization of BALB/cByJ mice with respiratory-type MHV-JHM, MHV-S, or enterotropic MHV-Y.
- Sham immunization with sterile tissue culture fluid as a control.
- Intranasal challenge with MHV-JHM or MHV-S at 30 days post-immunization.
- Assessment of MHV lesions in nose and liver, MHV titers in liver, and brainstem spongiform lesions.
- Quantification of serum antibodies to MHV-JHM and MHV-S using enzyme immunoassay.
Main Results:
- Mice immunized with MHV-JHM or MHV-S resisted challenge with the homologous MHV strain.
- MHV-S-immunized mice were susceptible to MHV-JHM challenge, indicating limited cross-protection.
- Mice immunized with enterotropic MHV-Y showed partial protection against antigenically related MHV-S.
- Serum antibody levels correlated with observed resistance, supporting the role of humoral immunity.
Conclusions:
- Challenge immunity to mouse hepatitis virus (MHV) is strong but highly specific to the immunizing virus strain.
- Cross-protection against different MHV strains is limited, emphasizing the need for strain-specific immunizations.
- These findings have implications for vaccine development and understanding coronavirus immunity in general.