Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal 2 challenge with pneumonia virus of mice

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Maunder, Helen E. ; Taylor, Geraldine ; Leppard, Keith ; Easton, A. J. (Andrew J.) (2015)

Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response isuch animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8+ T cell response and, to a lesser extent, a CD4+ T cell response. These findings suggest that protection induced by rAd5N was mediated by T-cells rather than serum antibody.
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