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Vi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vaccine (Vi-PS) in healthy adults subsequently challenged with Salmonella Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot assay. Immunization induced significant expansion of plasma cells in both vaccines with modest T follicular helper cell responses detectable after Vi-TT only. The Vi-specific IgG and IgM B cell response was considerably greater in magnitude in Vi-TT recipients. Intriguingly, a significant increase in a subset of IgA+ plasma cells expressing mucosal migratory markers α4β7 and CCR10 was observed in both vaccine groups, suggesting a gut-tropic, mucosal response is induced by Vi-vaccination. The total plasma cell response was significantly associated with protection against typhoid fever in Vi-TT vaccinees but not Vi-PS. IgA+ plasma cells were not significantly associated with protection for either vaccine, although a trend is seen for Vi-PS. Conversely, the IgA- fraction of the plasma cell response was only associated with protection in Vi-TT. In summary, these data indicate that a phenotypically heterogeneous response including both gut-homing and systemic antibody secreting cells may be critical for protection induced by Vi-TT vaccination.

Original publication

DOI

10.3389/fimmu.2020.574057

Type

Journal article

Journal

Front Immunol

Publication Date

2020

Volume

11

Keywords

CyTOF, ELISpot assay, Salmonella Typhi, Vi-conjugate vaccine, mass cytometry, typhoid fever, ADP-ribosyl Cyclase 1, Adult, B-Lymphocytes, Enzyme-Linked Immunospot Assay, Flow Cytometry, Humans, Immunoglobulin A, Immunologic Memory, Lymphocyte Activation, Membrane Glycoproteins, Plasma Cells, Polysaccharides, Bacterial, Salmonella typhi, T Follicular Helper Cells, Tetanus Toxoid, Typhoid Fever, Typhoid-Paratyphoid Vaccines, Vaccination, Vaccines, Conjugate