Mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and interferon-gamma receptor deficient mice

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 (IFN gamma) 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 IFN gamma, TNF-alpha, MIP-1 alpha, and MIP-2. Interestingly, responses of vaccinated IFN gamma receptor gene-deleted mice were indistinguishable from those of the wild type, suggesting that IFN gamma signaling may not be crucial for the generation of adaptive responses to pneumovirus infection in vivo. (c) 2006 Elsevier Ltd. All rights reserved.