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Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever.

ABSTRACT: 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.

SUBMITTER: Cross DL

PROVIDER: S-EPMC7793947 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever.

Cross Deborah L DL Verheul Marije K MK Leipold Michael D MD Obermoser Gerlinde G Jin Celina C Jones Elizabeth E Starr Joshua S JS Mohorianu Irina I Blohmke Christoph J CJ Maecker Holden T HT Napolitani Giorgio G Hill Jennifer J Pollard Andrew J AJ

Frontiers in immunology 20201203

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 <i>Salmonella</i> Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot as ...[more]

PMID: 33424833

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Project description:BackgroundA cluster-randomised trial of Vi-tetanus toxoid (Vi-TT) conjugate vaccine conducted in urban Bangladeshi children found a high level of direct protection by Vi-TT but no significant vaccine herd protection. We reassessed the trial using a "fried egg" analysis to evaluate whether herd protection might have been obscured by transmission of typhoid into the clusters from the outside.MethodsA participant- and observer-blind, cluster-randomised trial was conducted between February 14, 2018 and August 12, 2019 in three wards of Mirpur, a densely populated urban area of Dhaka, Bangladesh. Children 9 months to under 16 years of age in 150 geographic clusters, which had a total of 311,289 persons present at baseline or entering during follow-up, were randomised by cluster to a single-dose of Vi-TT or Japanese encephalitis (JE) vaccine. Vi-TT protection against typhoid fever, detected at 8 treatment centres serving the study population, was compared in the original clusters for the trial, and for progressively more central subclusters ("yolks" of the "fried egg") of the cluster residents. If transmission of typhoid into the clusters had diluted observed vaccine herd protection, we hypothesised that analysis of the innermost "yolks" would reveal vaccine herd protection that was not evident in analysis of the entire clusters. The trial is registered at www.isrctn.com as ISRCTN11643110.FindingsAt ≤18 months of follow-up, total vaccine effectiveness (protection of Vi-TT recipients relative to JE vaccine recipients) was 85% (95% CI: 76%, 90%); indirect effectiveness (protection of non-Vi-TT recipients in Vi-TT clusters relative to non-JE vaccine recipients in JE vaccine clusters) was 17% (95% CI: -13%, 40%); and overall effectiveness (protection of all residents in the Vi-TT clusters relative to all residents of the JE vaccine clusters) was 57% (95% CI: 44%, 66%). Analyses of subpopulations in inner 75%, 50% and 25% "yolks" of the clusters failed to reveal significant changes in any of these estimates.InterpretationOur analysis did not reveal Vi-TT herd protection in the trial. Consideration should be given to exploring whether targeting adults as well as children with Vi-TT yields appreciable levels of vaccine herd protection.FundingBill & Melinda Gates Foundation (OPP1151153, INV-025388).

Dataset Information

Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever.

Publications

Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever.

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