Oxford Vaccine Group, Department of Pediatrics, University of Oxford, Oxford, UK.
National Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK.
J Exp Med. 2021 Feb 1;218(2). doi: 10.1084/jem.20201116.
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.
伤寒 Vi 疫苗已被证明对生活在流行地区的儿童有效；然而，一个广泛接受的保护相关因素仍然有待确定。我们应用系统血清学方法，使用从参加实验性人体感染研究的参与者中获得的样本，确定 Vi 特异性血清学保护相关因素。参与者接种了 Vi-破伤风类毒素结合疫苗（Vi-TT）或未结合的 Vi-多糖疫苗，随后用伤寒沙门氏菌进行了挑战。多变量分析确定了 Vi-TT 和 Vi-PS 疫苗的独特保护特征，以及预测两组保护的共同特征。Vi IgA 数量和亲和力与伤寒沙门氏菌感染的保护有关，而 Vi IgG 反应的更高倍数增加与疾病严重程度降低有关。还确定了靶向抗体介导的功能反应，特别是中性粒细胞吞噬作用，作为保护特征的重要组成部分。这些体液标志物可用于评估和开发有效的 Vi 结合疫苗，并有助于加快在伤寒流行地区提供疫苗。
