The majority of vaccines currently available for the prevention of influenza A virus (IAV) in swine are formulated as whole-inactivated virus(es) (WIV) with adjuvant, and delivered by the intramuscular route. While WIV vaccines may provide protection against infection with strains closely related to those in the vaccine, they provide limited cross-protection. There are a large number of different strains of IAV currently circulating in US swine and therefore, cross-protection against more distantly related viruses is important. Live-attenuated influenza virus (LAIV) vaccines, delivered by the intranasal route have been shown to provide increased cross-protection when compared to WIV vaccines. In addition, replication-defective virus (RDV) vectors have been shown to provide cross-protection. However, the immune response after LAIV or RDV vaccination is different than that following WIV vaccination and immune assays typically used to predict cross-protection are inaccurate when applied to LAIV vaccines. Specifically, measurement of IAV-specific antibody in the serum using the hemagglutination inhibition (HI) assay does not accurately predict cross-protection. Because LAIV vaccines are delivered by the intranasal route (and some RDV vaccines are also) we evaluated the ability of mucosal antibody to predict cross-protective efficacy of LAIV and RDV vaccines. Groups of pigs were given either LAIV or RDV and then nasal wash and oral fluids were collected weekly for 6 weeks. Groups of pigs were then challenged with heterologous IAV and efficacy evaluated by reduction in nasal shedding of virus, virus load in the respiratory tract (trachea and lung), and protection against lung pathology. Our data indicate that oral fluids can serve as a useful sample source for evaluating the ability of LAIV to induce an immune response to IAV. In addition, IAV-specific IgA (measured in in oral fluids) were associated with protection against heterologous challenge.
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