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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and
John A Ellis1, Brittany V Martin, Cheryl Waldner
1Western Veterinary Medical College, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Abstract:
Protective mechanisms underlying the responses to mucosal vaccination are not yet clearly defined. Using the natural mouse pneumovirus pathogen, pneumonia virus of mice (PVM), we explore responses of wild type and interferon-gamma (IFNgamma) receptor gene-deleted mice to virulent challenge after mucosal vaccination with an attenuated virus strain. Serum neutralizing antibodies develop after intranasal inoculation with 30 pfu of attenuated, replication-competent PVM strain 15, which correlate with diminished gross and microscopic pulmonary pathology and protection from weight loss in response to subsequent challenge with the virulent parent PVM strain J3666. Virus replication in response to challenge was blunted in PVM strain 15 vaccinated mice, as was local production of secretory mediators IFNgamma, TNF-alpha, MIP-1 alpha, and MIP-2. Interestingly, responses of vaccinated IFNgamma receptor gene-deleted mice were indistinguishable from those of the wild type, suggesting that IFNgamma signaling may not be crucial for the generation of adaptive responses to pneumovirus infection in vivo.
Insights
Mucosal vaccination with an attenuated pneumonia virus of mice (PVM) strain induces protective immunity. Interferon-gamma (IFNγ) signaling is not essential for these adaptive immune responses against PVM.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Protective mechanisms of mucosal vaccination are not fully understood.
- Pneumonia virus of mice (PVM) is a natural pathogen used to study respiratory virus responses.
Purpose of the Study:
- To investigate the protective immune responses following mucosal vaccination against PVM.
- To determine the role of interferon-gamma (IFNγ) signaling in these responses.
Main Methods:
- Mice (wild type and IFNγ receptor gene-deleted) were intranasally vaccinated with attenuated PVM strain 15.
- Vaccinated mice were subsequently challenged with virulent PVM strain J3666.
- Immune responses, including antibody production, viral replication, and mediator release, were assessed.
Main Results:
- Mucosal vaccination with attenuated PVM induced serum neutralizing antibodies.
- Vaccination reduced pulmonary pathology, weight loss, and viral replication upon challenge.
- Local production of IFNγ, TNF-α, MIP-1α, and MIP-2 was blunted post-vaccination and challenge.
- IFNγ receptor gene-deleted mice showed responses similar to wild-type mice.
Conclusions:
- Mucosal vaccination with attenuated PVM confers protection against virulent PVM challenge.
- IFNγ signaling is not critical for the development of adaptive immunity to PVM in this model.
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