Persisting antibody responses to Vi polysaccharide-tetanus toxoid conjugate (Typbar TCV®) vaccine up to 7 years following primary vaccination of children < 2 years of age with, or without, a booster vaccination
Persisting antibody responses to Vi polysaccharide-tetanus toxoid conjugate (Typbar TCV®) vaccine up to 7 years following primary vaccination of children < 2 years of age with, or without, a booster vaccination
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DOI：
10.1016/j.vaccine.2021.07.073
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发表时间：
2021-10-16
期刊：
影响因子：
5.5
通讯作者：
Levine, Myron M.
中科院分区：
文献类型：
--
作者：
Vadrevu, Krishna Mohan;Raju, Dugyala;Levine, Myron M.
背景资料：327名6-23月龄儿童接种Vi多糖-破伤风类毒素结合疫苗后血清IgG抗Vi滴度（Typbar TCV（R）），其中193/327人在初次接种后2年接受了加强剂量。方法：使用三种不同的酶联免疫吸附试验（ELISA）监测初次免疫后3年、5年和7年加强和未加强儿童的抗Vi IgG：Vacczyme（TM）试剂盒ELISA（所有样本）;“Szu”ELISA（所有样本）和美国国家生物标准研究所NIBSC ELISA（子集）。分析的终点包括：持续性血清转换（滴度仍高于基线>= 4倍）、几何平均滴度（GMT）、接种后几何平均倍数上升和表现出推定保护性抗Vi水平的百分比（>= 2 μ g（Szu）/ml）使用Szu方法和美国国立卫生研究院IgG参考标准。在评估Typbar-TCV（R）刺激的抗Vi滴度升高的持续性时，根据最初入组的儿童是否在第720天加强免疫，以及他们是否在所有关键时间点提供血清，或者他们是否错过了一个或多个时间点，比较了四个亚组：i）在加强的参与者中，“所有样本组群”（ASC）包括86名儿童，他们在第42天、第720天（加强）、第762天（加强）、第762天（加强）提供血清。（加强后42天）、1095、1825和2555，以确定在7年内监测的完全依从的加强儿童队列中Vi抗体应答的动力学; ii）在未加强的受试者中，25名儿童的依从性全样本组在第0、42、720、1095、1825和2555天提供血清; iii）在加强免疫的儿童中，“任何可用样本”（AAS）亚组由在第0、42和720天以及在第762、1095、1825或2555天中的一天或多天提供血清但不是在所有这些时间点提供血清的加强免疫的儿童组成; iv）在未加强免疫的受试者中，还有47名儿童的任何可用样本亚组，他们在第0天和第42天提供血清，其中41名随后在第1095、1825和2555天中的一天或多天提供血清。在加强的ASC儿童（N = 86）中，Vacczyme（TM）GMT在第762天显著增加，并且在3、5和7年时保持为基线的32倍、14倍和10倍;在未加强的ASC儿童（N = 25）中，GMT分别保持在基线的21倍、8倍和5倍。初次接种后，72%和44%的未加强的ASC受试者（N = 25）分别在5年和7年时表现出Vacczyme（TM）的持续血清转化; ASC加强受试者的相应数字为84%和71%。在四个亚组中，加强受试者在大多数时间点显示出较高的持续血清转换患病率，到第7年时差距扩大，但不具有统计学显著性（第3年除外）。通过Szu和NIBSC ELISA测试，92-100%的未加强的ASC儿童在7岁时显示出持续的血清转化，100%也超过了Szu保护阈值。与入学时间相吻合，可能是明智的。Typbar TCV（R）是目前唯一一种WHO预认证的Vi结合疫苗，具有报道的效力、有效性和长期免疫原性结果。(C)2021作者（S）由爱思唯尔有限公司发布
Background: Serum IgG anti-Vi titers attained by 327 children 6-23 months of age immunized with Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar TCV (R)), of whom 193/327 received a booster dose 2 years post-primary vaccination, were previously reported.Methods: Anti-Vi IgG in boosted and unboosted children 3, 5, and 7 years post-primary immunization were monitored using three different enzyme-linked immunosorbent assays (ELISAs): Vacczyme (TM) kit ELISA (all specimens); "Szu" ELISA (all specimens), and National Institute of Biological Standards NIBSC ELISA (subset). Endpoints analyzed included: persisting seroconversion (titer remaining >= 4-fold above baseline), geometric mean titer (GMT), geometric mean-fold rise post-vaccination, and percent exhibiting putative protective anti-Vi level (>= 2 mu g(Szu)/ml) using Szu method and National Institutes of Health IgG reference standard.In assessing the persistence of elevated anti-Vi titers stimulated by Typbar-TCV (R), four subgroups were compared based on whether or not the initially enrolled children were boosted on day 720 and whether they provided serum on all key timepoints, or if they missed one or more timepoints: i) Among boosted participants, an "All Specimens Cohort" (ASC) comprised 86 children who provided sera on days 42, 720 (booster), 762 (42 days post-booster), 1095, 1825 and 2555, to define kinetics of the Vi antibody response in a fully compliant cohort of boosted children monitored over seven years; ii) Among non-boosted subjects, a compliant All Specimens Cohort of 25 children provided sera on days 0, 42, 720, 1095, 1825, and 2555; iii) Among boosted children, an "Any Available Specimen" (AAS) subgroup consisted of boosted children who provided sera on days 0, 42, and 720 days and also on one or more of days 762, 1095, 1825, or 2555 but not on all those time points; iv) Among the non-boosted subjects, there was also an Any Available Specimen subgroup of 47 children who provided sera on days 0 and 42, of whom 41 subsequently contributed sera on one or more of days 1095, 1825 and 2555.Results: Vacczyme (TM) GMTs among boosted ASC children (N = 86) increased significantly on day 762, and remained 32-fold, 14-fold, and 10-fold over baseline at 3, 5 and 7 years; among unboosted ASC children (N = 25), GMTs remained 21-fold, 8-fold and 5-fold over baseline, respectively. Post-primary vaccination, 72% and 44% of unboosted ASC subjects (N = 25) exhibited persisting seroconversion by Vacczyme (TM) at 5 and 7 years, respectively; the corresponding numbers for ASC boosted subjects were 84% and 71%. Amongst the four sub-groups, boosted subjects showed higher prevalence of persisting seroconversion at most time points with the gap widening by 7th year, though not statistically significant (except 3rd year). Tested by Szu and also NIBSC ELISAs, 92-100% of unboosted ASC children showed persisting seroconversion at 7 years with 100% also exceeding the Szu protective threshold.Conclusion: To extend protection, administering a booster of Typbar TCV (R) to children-5 years after their primary dose, i.e., coinciding with school entry, may be advisable. Typbar TCV (R) is presently the only WHO pre-qualified Vi conjugate vaccine with reported efficacy, effectiveness, and long-term immunogenicity findings. (C) 2021 The Author(s). Published by Elsevier Ltd.