Vi-specific serological correlates of protection for typhoid fever
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Typhoid Vi vaccines have been shown to be efficacious in children living in endemic regions; however, a widely accepted correlate of protection remains to be established. We applied a systems serology approach to identify Vi-specific serological correlates of protection using samples obtained from participants enrolled in an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) vaccines and were subsequently challenged with Salmonella Typhi bacteria. Multivariate analyses identified distinct protective signatures for Vi-TT and Vi-PS vaccines in addition to shared features that predicted protection across both groups. Vi IgA quantity and avidity correlated with protection from S. Typhi infection, whereas higher fold increases in Vi IgG responses were associated with reduced disease severity. Targeted antibody-mediated functional responses, particularly neutrophil phagocytosis, were also identified as important components of the protective signature. These humoral markers could be used to evaluate and develop efficacious Vi-conjugate vaccines and assist with accelerating vaccine availability to typhoid-endemic regions.
Date Issued
2020-11-12
Date Acceptance
2020-10-08
Citation
Journal of Experimental Medicine, 2020, 218 (2)
ISSN
0022-1007
Publisher
Rockefeller University Press
Journal / Book Title
Journal of Experimental Medicine
Volume
218
Issue
2
Copyright Statement
© 2020 Jin et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
License URL
Subjects
Adult
Bacterial Load
Humans
Immunity, Humoral
Immunogenicity, Vaccine
Immunoglobulin G
Time Factors
Typhoid Fever
Typhoid-Paratyphoid Vaccines
Vaccines, Conjugate
Humans
Typhoid Fever
Immunoglobulin G
Typhoid-Paratyphoid Vaccines
Vaccines, Conjugate
Time Factors
Adult
Immunity, Humoral
Bacterial Load
Immunogenicity, Vaccine
Immunology
11 Medical and Health Sciences
Publication Status
Published
Article Number
ARTN e20201116