Monoclonal Antibodies of a Diverse Isotype Induced by an O-Antigen Glycoconjugate Vaccine MediateIn VitroandIn VivoKilling of African Invasive Nontyphoidal Salmonella
Goh YS., Clare S., Micoli F., Saul A., Mastroeni P., MacLennan CA.
NontyphoidalSalmonella(NTS), particularlySalmonella entericaserovars 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–CRM197glycoconjugate 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 vitroandin vivokilling 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 ofSalmonellawith 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 vivofunctional 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–CRM197glycoconjugate vaccine can induce O-antigen-specific antibodies of different isotypes that exertin vitroandin vivokilling ofS. Typhimurium.