IgA and IgG1 Specific to Vi Polysaccharide of Salmonella Typhi Correlate With Protection Status in a Typhoid Fever Controlled Human Infection Model
IgA and IgG1 Specific to Vi Polysaccharide of Salmonella Typhi Correlate With Protection Status in a Typhoid Fever Controlled Human Infection Model
复制标题
DOI：
10.3389/fimmu.2019.02582
复制
发表时间：
2019-11-01
影响因子：
7.3
通讯作者：
Tomaras, Georgia D.
中科院分区：
文献类型：
--
作者：
Dahora, Lindsay C.;Jin, Celina;Tomaras, Georgia D.
使用Vi荚膜多糖（一种T细胞非依赖性抗原）接种伤寒沙门氏菌疫苗可以预防伤寒的发展。这意味着单独的Vi抗体可以在不存在T细胞介导的免疫应答的情况下进行保护;然而，保护性Vi抗体尚未得到充分表征。我们假设疫苗引起的抗体的生物物理性质的变化，包括亚类分布和亲合力，可能会影响保护性结果。为了探讨抗体特性与伤寒保护之间的关系，我们分析了使用对照人类感染模型（CHIM）的疫苗效力（VE）试验参与者的体液应答，这些参与者接受纯化Vi多糖（Vi-PS）或Vi破伤风类毒素缀合物（Vi-TT）疫苗，然后用活S.伤寒我们测定了Vi伊加和IgG亚类抗体的亲合力、总体幅度和从免疫前至攻毒当天疫苗诱导的幅度倍数变化。在接受Vi-PS疫苗的那些人中，与发生疾病（“诊断”）的那些个体相比，受保护个体的Vi伊加幅度（FDR p = 0.01）和倍数变化（FDR p = 0.02）显著更高。在Vi-TT疫苗组中，受保护个体的应答比诊断的Vi-TT疫苗接种者具有更高的Vi伊加倍数变化（FDR p = 0.06）和更高的Vi IgG 1亲合力（FDR p = 0.058），尽管这些发现在p < 0.05时不显著。总体而言，Vi-PS和Vi-TT疫苗之间的保护性抗体特征不同，因此，我们得出结论，尽管观察到Vi-PS和Vi-TT疫苗具有相似的效力，但这些疫苗可能通过不同的机制提供保护。这些数据将为伤寒保护机制的研究提供信息，包括抗体效应子功能的鉴定，以及为未来的疫苗接种策略提供信息。
Vaccination against Salmonella Typhi using the Vi capsular polysaccharide, a T-cell independent antigen, can protect from the development of typhoid fever. This implies that antibodies to Vi alone can protect in the absence of a T cell-mediated immune response; however, protective Vi antibodies have not been well-characterized. We hypothesized that variability in the biophysical properties of vaccine-elicited antibodies, including subclass distribution and avidity, may impact protective outcomes. To interrogate the relationship between antibody properties and protection against typhoid fever, we analyzed humoral responses from participants in a vaccine efficacy (VE) trial using a controlled human infection model (CHIM) who received either a purified Vi polysaccharide (Vi-PS) or Vi tetanus toxoid conjugate (Vi-TT) vaccine followed by oral challenge with live S. Typhi. We determined the avidity, overall magnitude, and vaccine-induced fold-change in magnitude from before immunization to day of challenge of Vi IgA and IgG subclass antibodies. Amongst those who received the Vi-PS vaccine, Vi IgA magnitude (FDR p = 0.01) and fold-change (FDR p = 0.02) were significantly higher in protected individuals compared with those individuals who developed disease ("diagnosed"). In the Vi-TT vaccine group, the responses of protected individuals had higher fold-change in Vi IgA (FDR p = 0.06) and higher Vi IgG1 avidity (FDR p = 0.058) than the diagnosed Vi-TT vaccinees, though these findings were not significant at p < 0.05. Overall, protective antibody signatures differed between the Vi-PS and Vi-TT vaccines, thus, we conclude that although the Vi-PS and Vi-TT vaccines were observed to have similar efficacies, these vaccines may protect through different mechanisms. These data will inform studies on mechanisms of protection against typhoid fever, including identification of antibody effector functions, as well as informing future vaccination strategies.