Distinct protective humoral signatures are induced by Vi-conjugate and Vi-polysaccharide vaccines. Shared humoral features across both vaccines suggest that protection against typhoid fever is mediated through a combination of qualitative features of the polyclonal humoral response (avidity and innate immune cell functional responses) in addition to antibody quantity. 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.
【초록키워드】 Vaccine, Vaccines, serology, antibody, children, disease severity, neutrophil, Infection, IgA, Fever, Bacteria, phagocytosis, serological, Protective, Salmonella, marker, Endemic, Combination, Analysis, humoral, IgG response, both groups, multivariate, human infection, participant, vaccine availability, component, regions, responses, approach, typhoid, feature, polyclonal, enrolled, shown, predicted, identify, develop, addition, applied, reduced, functional, correlated, assist, increases in, innate immune cell, used to evaluate, 【제목키워드】 Fever, serological,