Salmonella typhimurium infection in calves: cell-mediated and humoral immune reactions before and after challenge with live virulent bacteria in calves given live or inactivated vaccines

Abstract

Groups of six calves, 4 to 5 weeks old, were vaccinated either orally with a live auxotrophic Salmonella typhimurium (O-antigen 1,4,12) SL1479 vaccine (10(8) bacteria on day zero, 10(10) bacteria on days 7 and 14) or subcutaneously with a heat-inactivated (56 degrees C, 30 min) S. typhimurium SVA1232 vaccine (10(10) bacteria suspended in 30% [vol/vol] aluminum hydroxide on days zero, 7, and 14). The calves were then orally challenged with either 10(6) (approximately 100 X the 25% lethal dose) or 10(9) (approximately 100,000 X the 25% lethal dose) live bacteria of the calf-virulent S. typhimurium SVA44 strain. The immune reactivity of these calves and of nonvaccinated control calves was followed before and after the challenge infection up to 42 days by (i) intradermal injection of S. typhimurium crude extract, outer membrane protein preparation (porins), and lipopolysaccharide (LPS), (ii) in vitro stimulation of peripheral blood lymphocytes estimated by using uptake of [3H]thymidine, with S. typhimurium crude extract, porins, LPS, and polysaccharide (O-antigenic polysaccharide chain free of lipid A), and Salmonella sp. serotype thompson (O-antigen 6,7) strain IS40 LPS and polysaccharide, and (iii) estimation of the class-specific immunoglobulin G (IgG) and IgM antibody responses against S. typhimurium LPS and porins, and Salmonella sp. serotype thompson LPS. The immune studies showed that in calves given the live vaccine orally, the skin test reactivity and lymphocyte stimulation indices were significantly higher (P values ranging from less than 0.025 to less than 0.0005) against homologous, but not heterologous, antigens than those seen in calves given the heat-inactivated vaccine subcutaneously. In contrast, the IgG and IgM antibody titers against homologous LPS and porins were significantly higher (P less than 0.0005) in sera collected on day 21 from calves given the heat-inactivated vaccine than in calves given the live vaccine. After the oral challenge, calves given the live vaccine showed reduced cell-mediated immune reactions, in agreement with the observation that the host defense could eradicate the challenge organism, whereas calves given the heat-inactivated vaccine showed significantly increased cell-mediated immune reactions (P values ranging from less than 0.025 to less than 0.005), in agreement with the observation that in these calves, the challenge strain caused enteritis as well as systemic invasion. The increased cell-mediated immune reactivity in calves given the live vaccine correlated well with the excellent protection against challenge infection seen in these animals.