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 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.

Automated summary

Typhoid Vi vaccines have shown efficacy in children living in endemic regions, but a clear correlate of protection is still being established. Vi IgA quantity and avidity, as well as higher fold increases in Vi IgG responses, are correlated with protection from S. Typhi infection, while targeted antibody-mediated functional responses play a key role in the protective signature. These humoral markers can help evaluate and develop effective Vi-conjugate vaccines for typhoid endemic regions.