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Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing.

Published version
Peer-reviewed

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Authors

Goh, Yun Shan 
Armour, Kathryn L 
Clark, Michael R 
Grant, Andrew J 

Abstract

Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease.

Description

Keywords

Antibody, Flagella, IgG subclasses, Opsonisation, Phagocytosis

Journal Title

J Vaccines Vaccin

Conference Name

Journal ISSN

2157-7560
2157-7560

Volume Title

7

Publisher

OMICS Publishing Group
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/I002189/1)
Medical Research Council (G1100102)
Medical Research Council (G0001245)
Medical Research Council (G0801161)
Wellcome Trust (081743/Z/06/Z)
This work was supported by grants from the Wellcome Trust (081743/Z/06/Z) awarded to P.M. and A.J.G and from the Medical Research Council G0801161 awarded to A.J.G. and P.M.