Antibody-Based Correlates of Protection against Cholera: Analysis of a Challenge Study of a Cholera-Naive Population
Antibody-Based Correlates of Protection against Cholera: Analysis of a Challenge Study of a Cholera-Naive Population
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DOI：
10.1128/cvi.00098-17
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发表时间：
2017-08-01
影响因子：
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通讯作者：
Gurwith, Marc
中科院分区：
文献类型：
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作者：
Haney, Douglas J.;Lock, Michael D.;Gurwith, Marc
保护的免疫学相关性可用于推断疫苗对无法进行挑战试验或实地研究的人群的效力。在最近的一项霍乱挑战试验中（W. H. Chen等人，临床感染病62:1329-1335,2016,https://doi.org/10.1093/cid/ciw145）， 134名北美霍乱初发志愿者被随机分配接受活减毒单剂量霍乱疫苗CVD（疫苗开发中心）103-HgR或安慰剂，并在治疗后10天评估针对经典Inaba菌株的杀弧菌抗体滴度。在免疫评估之后，每个受试者摄入一定量的强毒霍乱弧菌O1 El - Tor Inaba。该试验的数据表明，攻击前疫苗诱导的杀弧菌抗体滴度的增加与保护密切相关：51/51接种后杀弧菌抗体滴度>= 2560的疫苗接种者对中度/重度腹泻有保护作用，60/62接种者血清转化或经历4倍或更多的杀弧菌抗体滴度相对于接种前水平的保护。在一些安慰剂受试者中观察到非典型的高杀弧菌抗体滴度；这些个体的保护是有限的，与相同接种后滴度的疫苗接种者所经历的保护水平有很大不同。由于66名安慰剂接受者中只有1人出现血清转换，因此发现血清转换与疫苗接种唯一相关，并且对可能导致滴度升高但与保护作用相关性较弱的因素的影响不敏感。因此，在推断霍乱初发人群的疫苗效力时，发现杀弧菌抗体血清转换比杀弧菌抗体滴度更好，因为基于暴露于霍乱弧菌的研究是不切实际的。
Immunologic correlates of protection can be used to infer vaccine efficacy for populations in which challenge trials or field studies are infeasible. In a recent cholera challenge trial (W. H. Chen et al., Clin Infect Dis 62: 1329-1335, 2016,https://doi.org/10.1093/cid/ciw145), 134 North American cholera-naive volunteers were randomized to receive either the live, attenuated single-dose cholera vaccine CVD (Center for Vaccine Development) 103-HgR or placebo, and the titers of vibriocidal antibodies against the classical Inaba strain were assessed at 10 days after treatment. Subsequent to the immunologic evaluation, each subject ingested a fixed quantity of virulent Vibrio cholerae O1 El Tor Inaba. Data from this trial suggest that the vaccine-induced increase in the vibriocidal antibody titer prior to challenge is tightly linked with protection: 51/51 vaccinees with postvaccination vibriocidal antibody titers of >= 2,560 were protected against moderate/severe diarrhea, and 60/62 vaccinees who seroconverted or experienced a 4-fold or greater increase in vibriocidal antibody titer relative to prevaccination levels were similarly protected. Atypically high vibriocidal antibody titers were observed in some placebo subjects; protection was limited in these individuals and differed substantially from the level of protection experienced by vaccinees with the same postvaccination titers. Since only 1 of 66 placebo recipients experienced seroconversion, seroconversion was found to be uniquely associated with vaccination and insensitive to the effects of factors that can cause titers to be elevated but are weakly associated with protection. Thus, vibriocidal antibody seroconversion was found to be better than the vibriocidal antibody titer for inferring vaccine efficacy in cholera-naive populations for which studies based upon exposure to V. cholerae are impractical.