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NontyphoidalSalmonella (NTS), particularlySalmonella enterica serovars Typhimurium and Enteritidis, is responsible for a major global burden of invasive disease with high associated case-fatality rates. We recently reported the development of a candidate O-antigen–CRM197 glycoconjugate vaccine againstS. Typhimurium. Here, using a panel of mouse monoclonal antibodies generated by the vaccine, we examined the relative efficiency of different antibody isotypes specific for the O:4 antigen ofS . Typhimurium to effectin vitro andin vivo killing of the invasive AfricanS . Typhimurium strain D23580. All O:4-specific antibody isotypes could mediate cell-free killing and phagocytosis ofS . Typhimurium by mouse blood cells. Opsonization ofSalmonella with O:4-specific IgA, IgG1, IgG2a, and IgG2b, but not IgM, resulted in cell-dependent bacterial killing. At high concentrations, O:4-specific antibodies inhibited both cell-free complement-mediated and cell-dependent opsonophagocytic killing ofS . Typhimuriumin vitro . Using passive immunization in mice, the O:4-specific antibodies providedin vivo functional activity by decreasing the bacterial load in the blood and tissues, with IgG2a and IgG2b being the most effective isotypes. In conclusion, an O-antigen–CRM197 glycoconjugate vaccine can induce O-antigen-specific antibodies of different isotypes that exertin vitro andin vivo killing ofS . Typhimurium.

infection and immunity

Monoclonal Antibodies of a Diverse Isotype Induced by an O-Antigen Glycoconjugate Vaccine Mediate <i>In Vitro</i> and <i>In Vivo</i> Killing of African Invasive Nontyphoidal Salmonella

Monoclonal Antibodies of a Diverse Isotype Induced by an O-Antigen Glycoconjugate Vaccine Mediate In Vitro and In Vivo Killing of African Invasive Nontyphoidal Salmonella