Vi-specific serological correlates of protection for typhoid fever

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 p...

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Bibliographic Details
Published in:	The Journal of experimental medicine 2021-02, Vol.218 (2)
Main Authors:	Jin, Celina, Hill, Jennifer, Gunn, Bronwyn M, Yu, Wen-Han, Dahora, Lindsay C, Jones, Elizabeth, Johnson, Mari, Gibani, Malick M, Spreng, Rachel L, Alam, S Munir, Nebykova, Anna, Juel, Helene B, Dennison, S Moses, Seaton, Kelly E, Fallon, Jonathan K, Tomaras, Georgia D, Alter, Galit, Pollard, Andrew J
Format:	Article
Language:	eng
Subjects:	Adult Bacterial Load Humans Immunity, Humoral Immunogenicity, Vaccine Immunoglobulin G - blood Infectious Disease and Host Defense Time Factors Typhoid Fever - immunology Typhoid Fever - prevention & control Typhoid-Paratyphoid Vaccines - immunology Typhoid-Paratyphoid Vaccines - pharmacology Vaccines, Conjugate - immunology Vaccines, Conjugate - pharmacology
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Summary:	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.
ISSN:	0022-1007 1540-9538