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首页> 外文期刊>Infection and immunity >Antibodies in Action: Role of Human Opsonins in Killing Salmonella enterica Serovar Typhi
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Antibodies in Action: Role of Human Opsonins in Killing Salmonella enterica Serovar Typhi

机译：行动中的抗体：人调理素在杀死肠炎沙门氏菌血清型伤寒中的作用

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Although vaccines have been available for over a century, a correlate of protection for typhoid fever has yet to be identified. Antibodies are produced in response to typhoid infection and vaccination and are generally used as the gold standard for determining vaccine immunogenicity, even though their role in clearance of Salmonella enterica serovar Typhi infections is poorly defined. Here, we describe the first functional characterization of S. Typhi-specific antibodies following vaccination with a new vaccine, M01ZH09 (Ty2 ΔaroC ΔssaV). We determined that postvaccination sera increased the uptake of wild-type S. Typhi by human macrophages up to 2.3-fold relative to prevaccination (day 0) or placebo samples. These results were recapitulated using immunoglobulins purified from postvaccination serum, demonstrating that antibodies were largely responsible for increases in uptake. Imaging verified that macrophages internalized 2- to 9.5-fold more S. Typhi when the bacteria were opsonized with postvaccination sera than when the bacteria were opsonized with day 0 or placebo sera. Once inside macrophages, the survival of S. Typhi was reduced as much as 50% when opsonized with postvaccination sera relative to day 0 or placebo serum samples. Lastly, bactericidal assays indicated that antibodies generated postvaccination were recognized by complement factors and assisted in killing S. Typhi: mean postvaccination bactericidal antibody titers were higher at all time points than placebo and day 0 titers. These data clearly demonstrate that there are at least two mechanisms by which antibodies facilitate killing of S. Typhi. Future work could lead to improved immunogenicity tests associated with vaccine efficacy and the identification of correlates of protection against typhoid fever.
机译：尽管疫苗已经使用了一个多世纪，但尚未发现伤寒保护的相关因素。抗体是针对伤寒和疫苗接种而产生的，尽管对清除肠炎沙门氏菌伤寒沙门氏菌感染的作用尚不明确，但通常被用作确定疫苗免疫原性的金标准。在这里，我们描述了新型疫苗M01ZH09（Ty2Δ aroC Δ ssaV ）。我们确定了疫苗接种后的血清使人巨噬细胞对野生型 S。 Typhi的摄取相对于疫苗接种前（第0天）或安慰剂样品增加了2.3倍。使用从疫苗接种后血清中纯化的免疫球蛋白概括了这些结果，表明抗体是摄取增加的主要原因。影像学证实，与接种0天或安慰剂血清进行调理后相比，用接种疫苗后血清调理细菌时巨噬细胞内在的 S。 Typhi多2到9.5倍。一旦进入巨噬细胞，相对于第0天或安慰剂血清样品，经接种疫苗血清调和后， S。 Typhi的存活率降低多达50％。最后，杀菌分析表明，疫苗接种后产生的抗体可被补体因子识别并有助于杀死 S Typhi：疫苗接种后的平均杀菌抗体滴度在所有时间点均高于安慰剂和0天滴度。这些数据清楚地表明，至少有两种机制可通过抗体促进杀死 S。 Typhi。未来的工作可能会导致改善与疫苗效力相关的免疫原性测试，并确定针对伤寒的保护相关性。

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