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BACKGROUND: Oral vaccination with live-attenuated Salmonella Typhi strain Ty21a is modestly efficacious, but the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed. METHODS: We vaccinated healthy adults with Ty21a and assessed humoral and cellular immunity in vaccinated volunteers and controls after 18 days. Immunoglobulin levels were assessed in peripheral blood by an enzyme-linked immunosorbent assay. Cellular responses were assessed in peripheral blood and at the duodenal and colonic mucosa by flow cytometry. RESULTS: We demonstrate the generation of Ty21a-responsive and heterologous influenza virus-responsive CD4(+) and CD8(+) T cells at the duodenal mucosa. All duodenal responses were consistently correlated, and no responses were observed at the colonic mucosa. Peripheral anti-lipopolysaccharide immunoglobulin G and immunoglobulin A responses were significantly correlated with duodenal responses. The assessment of integrin β7 expression intensity among peripheral and duodenal T-cell subsets revealed varied capacities for mucosal homing and residence. CONCLUSIONS: The breadth of duodenal cellular responses was not reflected peripherally. The direct evaluation of mucosal immune defense may yield functional correlates of protection and could provide insight into mechanisms that may be manipulated to enhance vaccine immunogenicity.

Original publication

DOI

10.1093/infdis/jiw030

Type

Journal article

Journal

J Infect Dis

Publication Date

01/06/2016

Volume

213

Pages

1809 - 1819

Keywords

Salmonella, T cells, Ty21a, cellular immunity, cytokines, heterologous immunity, humoral immunity, immunoglobulins, typhoid, Administration, Oral, Adult, Antibodies, Bacterial, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunity, Cellular, Immunity, Humoral, Immunogenicity, Vaccine, Intestinal Mucosa, Male, Orthomyxoviridae, Polysaccharides, Bacterial, Salmonella typhi, Typhoid-Paratyphoid Vaccines, Vaccines, Attenuated, Young Adult