BHV-1 GLYCOPROTEIN-1 AND RECOMBINANT INTERLEUKIN-1-BETA EFFICIENTLY ELICIT MUCOSAL IGA RESPONSE

The mucosal immune response to most soluble antigens administered directly to the mucosal system is low and requires a large amount of antigen and frequent vaccinations. In this study we tested whether immunizing cattle at a site which shares lymphatic drainage with the nasal mucosa could prime local mucosal immunity. We further tested whether recombinant bovine IL-1 beta (rBoIL-1 beta could potentiate the induction of mucosal immunity. Animals were immunized subcutaneously at the base of the ear (s.e.) with recombinant bovine herpesvirus-1 (BHV-1) envelope glycoprotein I (gI) (35 mu g animal(-1)) emulsified in incomplete Freund's adjuvant with or without rBoIL-1 beta (500 ng kg(-1)) followed by a second immunization 42 days later. Animals were challenged with virulent BHV-1 intranasally 42 days after the second immunization. Mucosal IgA from the nares was induced after only one immunization, and enhanced by boosting. rBoIL-1 beta treated animals had higher levels of BHV-1 specific nasal IgA (p<0.01) and serum neutralizing antibody (p<0.05). rBolL-1 beta-treated animals also had increased numbers of surface IgA+ (p<0.05) and IgG1(+) (p<0.001) B cells after in vitro antigen (gI) stimulation of peripheral blood lymphocytes suggesting that there was a greater expension of IgA+ and IgG1+ B cells in rBoIL-1 beta created animals. When challenged with BHV-1, 3 of 4 animals in the gI-rBoIL-1 beta group were fully protected from viral replication in the nares, while only I of 4 animals receiving gI alone was protected. Our novel findings suggested that immunization at sites that share lymphatic drainage with mucosal surfaces is an efficient way for stimulating the mucosal IgA response. Furthermore, rBolL-1 beta can be a potent stimulator of this mucosal and systemic IgA production.