Monoclonal antibodies of diverse isotype induced by an O-antigen glycoconjugate vaccine mediate in vitro and in vivo killing of African invasive nontyphoidal Salmonella
Goh, Yun Shan
MacLennan, Calman A
Infection and Immunity
American Society for Microbiology
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Goh, Y. S., Clare, S., Micoli, F., Saul, A., Mastroeni, P., & MacLennan, C. A. (2015). Monoclonal antibodies of diverse isotype induced by an O-antigen glycoconjugate vaccine mediate in vitro and in vivo killing of African invasive nontyphoidal Salmonella. Infection and Immunity, 83 3722-3731. https://doi.org/10.1128/IAI.00547-15
Nontyphoidal Salmonellae (NTS), particularly S. enterica serovars Typhimurium and Enteritidis, are responsible for a major global burden of invasive disease with high associated case-fatality rate. We recently reported the development of a candidate O-antigen-CRM_197 glycoconjugate vaccine against S. 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 S. Typhimurium to effect in vitro and in vivo killing of the invasive African S. Typhimurium D23580. All O:4-specific antibody isotypes could mediate cell-free killing and phagocytosis of S. Typhimurium by mouse blood cells. Opsonization of Salmonella 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 S. Typhimurium in vitro. Using passive immunization in mice, the O:4-specific antibodies provided in 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-CRM_197 glycoconjugate vaccine can induce O-antigen specific antibodies of different isotypes that exert in vitro and in vivo killing of S. Typhimurium.
Salmonella, Typhimurium, Nontyphoidal, Antibody, Glycoconjugate, Vaccine, Lipopolysaccharide, O-antigen, Africa
This work was supported by a European Union FP7 Industry and Academia Partnerships and Pathways award, GENDRIVAX (Genome-driven vaccine development for bacterial infections). This is a collaboration between the Novartis Vaccines Institute for Global Health, Wellcome Trust Sanger Institute, Swiss Tropical and Public Health Institute and Kenyan Medical Research Institute [grant number 251522]. CAM is the recipient of a Clinical Research Fellowship from GlaxoSmithKline.
External DOI: https://doi.org/10.1128/IAI.00547-15
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248932
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Licence URL: http://creativecommons.org/licenses/by-nc-sa/2.0/uk/