Rotavirus vaccines and impact of maternal antibodies and cytokines on neonatal immune responses in swine
Rotavirus is the major cause of gastroenteritis in infants, young children and animals worldwide. Variable efficacies in rotavirus vaccine trials were attributed to maternal antibody (MatAb) interference. We demonstrated first that a vaccine consisting of oral (PO) attenuated human rotavirus (AttHRV) and oral 2/6-virus-like-particles (VLP) with immunostimulating complexes (ISCOM) (AttHRV/PO-VLP) induced high protection rates against virus shedding and diarrhea, and high serum IgA, IgG and intestinal IgA antibody titers in seronegative gnotobiotic pigs. We next investigated effects of different titers of MatAb on protection and immune responses to the above vaccine but with VLP given intranasally (IN) [(AttHRV/IN-VLP) or IN VLP/ISCOM (VLP3x) vaccines]. High titer circulating MatAb contributed to partial protection against HRV challenge; however, MatAb interference led to no or low intestinal IgM, IgA and IgG antibody titers and significantly reduced intestinal IgA and IgG effector and memory B cell responses in the AttHRV/INVLP pigs pre- and post-challenge. Suppression was not alleviated by extending the vaccination/challenge interval from 28 to 42 days. Suppression by high titer MatAb was also occurred in VLP3x vaccinated pigs, indicated by reduced intestinal IgG antibody secreting cells (ASC), serum and intestinal IgA antibodies and pre-challenge memory B cell responses. Low titer (Lo) MatAb had both enhancing and suppressing effects on B cell responses, depending on tissue, antibody isotype and vaccine. Differential effects of LoMatAb on IgA responses suggest that LoMatAb did not suppress induction of IgA ASC and memory B cells in the induction site (ileum) but impaired homing of activated B cells to secondary lymphoid or effector tissues, reducing IgA ASC and antibodies at these sites. Finally we investigated cytokines transferred from sow colostrum/milk to their suckling and weaned pigs. The peak mean cytokine concentrations (IL-4>TGF-b1>IL-6>IL-12>IFN-g>IL-10) in pig sera were detected at 1-2 days post-partum. High IL-4 and TGF-b1 concentrations in serum of suckling pigs may explain the Th2-biased neonatal immune responses. Increased serum IL-6 and IL-12 concentrations in weaned pigs suggest acclimation to post-suckling microbial flora. This knowledge provides a basis for future studies of influences of maternally-derived cytokines, in addition to MatAb, on development of the neonatal immune system.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:rotavirus vaccine maternal antibodies cytokines interference immune responses pigs gnotobiotic
Date of Publication:01/01/2005