Invasive African nontyphoidal Salmonella requires high levels of complement for cell-free antibody-dependent killing
Invasive African nontyphoidal Salmonella requires high levels of complement for cell-free antibody-dependent killing
复制标题
DOI：
10.1016/j.jim.2012.10.005
复制
发表时间：
2013-01-01
影响因子：
2.2
通讯作者：
MacLennan, Calman A.
中科院分区：
文献类型：
--
作者：
Goh, Yun Shan;MacLennan, Calman A.
非伤寒沙门氏菌（NTS），特别是鼠伤寒沙门氏菌，是非洲侵袭性菌血症的主要原因。尽管如此，目前还没有针对NTS的疫苗可用于人类。如果要及时开发NTS疫苗，则需要开发测定法以评估其体内功效。在临床前模型中评估候选疫苗的潜在功效对于概念验证非常重要，并可以减少临床试验中疫苗的损耗。血清杀菌试验（SBA）通常用于评估疫苗诱导的针对革兰氏阴性菌的抗体应答的功能活性，结果以可实现细菌杀灭的最大血清稀释度给出。以前，我们已经发现了证据的保护作用，抗体诱导的补体介导的杀伤NTS在非洲儿童使用未稀释的全血清SBA。然而，稀释的人血清中的内源性补体是有限的，不足以对S.鼠伤寒沙门氏菌超过2倍稀释。在目前的研究中，我们研究了使用幼兔血清（BRS）作为外源性补体来源的SBA对NTS的需求。我们发现抗体介导的杀菌活性所需的补体量对于侵袭性的非洲沙门氏菌来说要高得多。鼠伤寒沙门氏菌分离株D23580与实验室S.鼠伤寒LT2和甲型副伤寒沙门氏菌CVD1901。20% BRS足以杀死LT 2和CVD1901，而杀死D23580需要75% BRS。我们的研究结果表明，一个浓度的外源性补体是不适合SBA对所有沙门氏菌分离株。为了开发SBA来评估沙门氏菌疫苗的体内效力，有必要优化疫苗针对的沙门氏菌分离株的测定。(C)2012爱思唯尔有限公司版权所有。
Nontyphoidal isolates of Salmonella (NTS), particularly Salmonella Typhimurium, are a major cause of invasive bacteremia in Africa. Despite this, no vaccine against NTS is currently available for use in humans. If a NTS vaccine is to be developed in a timely manner, there is a need to develop assays to assess its in vivo efficacy. Assessment of potential efficacy of candidate vaccines in preclinical models is important for proof-of-concept and reduces attrition of vaccines in clinical trials. Serum bactericidal assays (SBA) are often used to assess the functional activity of vaccine-induced antibody responses targeted against Gram-negative bacteria with results given as the maximum dilution of serum that can effect bacterial killing. Previously we have found evidence for a protective role for antibody-induced complement-mediated killing of NTS in African children using an undiluted whole serum SBA. However, endogenous complement in diluted human sera is limiting and insufficient to effect bactericidal activity against S. Typhimurium beyond two two-fold dilutions. In the current study, we examined the requirements for SBA against NTS using baby rabbit serum (BRS) as an exogenous source of complement. We found that the amount of complement required for antibody-mediated bactericidal activity is much higher for the invasive African S. Typhimurium isolate D23580, compared with the laboratory S. Typhimurium LT2 and Salmonella Paratyphi A CVD1901. While 20% BRS was sufficient to kill LT2 and CVD1901, 75% BRS was needed to kill D23580. Our findings demonstrate that one concentration of exogenous complement is not suitable for SBA against all Salmonella isolates. To develop SBA to assess the in vivo efficacy of Salmonella vaccines, it is necessary to optimize the assay for the Salmonella isolates against which the vaccine is targeted. (C) 2012 Elsevier B.V. All rights reserved.