Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, United Kingdom.
Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover.
Clin Infect Dis. 2019 Aug 16;69(5):786-794. doi: 10.1093/cid/ciy1004.
In a 2012 Phase II clinical trial, 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single intranasally-administered dose of either trivalent, Russian-backbone, live, attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09, relative to the A/H3N2 and B strains. This post hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that preexisting humoral and mucosal immunity may influence viral recovery and immune responses after LAIV receipt.
We used logistic regressions to evaluate the relations between markers of preexisting immunity (ie, hemagglutination inhibition [HAI], microneutralization, and immunoglobulin G and immunoglobulin A (both serum and mucosal antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (ie, <10 versus ≥10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses, measured between days 0 and 21 post-vaccination.
Higher levels of preexisting immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all 3 strains, the magnitudes of immune responses were most pronounced in children with no evidence of preexisting HAI and in those with detectable virus.
The results provide evidence for a bidirectional association between viral replication and immunity, and underscore the importance of accounting for preexisting immunity when evaluating virologic and immunologic responses to LAIVs.
NCT01625689.
在 2012 年的一项 II 期临床试验中，300 名 24 至 59 月龄、既往无流感疫苗暴露的孟加拉国儿童被随机分配接受单次鼻腔内接种三价、俄罗斯骨架、活、减毒流感疫苗（LAIV）或安慰剂。方案定义的分析结果在相关论文中报告，与 A/H3N2 和 B 株相比，A/H1N1pdm09 的病毒检出率和免疫原性降低。本试验数据的事后分析旨在通过检验以下假设来研究 LAIV 株的差异，即预先存在的体液和黏膜免疫可能影响 LAIV 接种后的病毒恢复和免疫反应：预先存在的免疫（即血凝抑制[HAI]、微量中和和免疫球蛋白 G 和免疫球蛋白 A（血清和黏膜抗体））与接种后一周内 LAIV 病毒恢复之间存在关系。然后，我们通过基线 HAI 滴度（即<10 与≥10）和第 1 周病毒恢复情况来检测 LAIV 诱导的血清和黏膜免疫反应的潜在效应修饰作用，该反应在接种后 0 至 21 天之间进行测量。
针对流感 A/H3N2 和 B 的预先存在的更高水平的免疫与接种 LAIV 后病毒脱落的特定株特异性预防密切相关。虽然观察到了针对所有 3 种株的 LAIV 免疫原性证据，但在没有预先存在的 HAI 证据和可检测到病毒的儿童中，免疫反应的幅度最大。
这些结果提供了病毒复制和免疫之间存在双向关联的证据，并强调了在评估 LAIV 的病毒学和免疫学反应时，考虑预先存在的免疫的重要性。
NCT01625689。
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