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<jats:p>Nontyphoidal<jats:named-content content-type="genus-species">Salmonella</jats:named-content>(NTS), particularly<jats:named-content content-type="genus-species">Salmonella enterica</jats:named-content>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–CRM<jats:sub>197</jats:sub>glycoconjugate vaccine against<jats:italic>S.</jats:italic>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 of<jats:italic>S</jats:italic>. Typhimurium to effect<jats:italic>in vitro</jats:italic>and<jats:italic>in vivo</jats:italic>killing of the invasive African<jats:italic>S</jats:italic>. Typhimurium strain D23580. All O:4-specific antibody isotypes could mediate cell-free killing and phagocytosis of<jats:italic>S</jats:italic>. Typhimurium by mouse blood cells. Opsonization of<jats:named-content content-type="genus-species">Salmonella</jats:named-content>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 of<jats:italic>S</jats:italic>. Typhimurium<jats:italic>in vitro</jats:italic>. Using passive immunization in mice, the O:4-specific antibodies provided<jats:italic>in vivo</jats:italic>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–CRM<jats:sub>197</jats:sub>glycoconjugate vaccine can induce O-antigen-specific antibodies of different isotypes that exert<jats:italic>in vitro</jats:italic>and<jats:italic>in vivo</jats:italic>killing of<jats:italic>S</jats:italic>. Typhimurium.</jats:p>

Original publication

DOI

10.1128/iai.00547-15

Type

Journal article

Journal

Infection and Immunity

Publisher

American Society for Microbiology

Publication Date

09/2015

Volume

83

Pages

3722 - 3731