Communicable Disease Prevention and Control Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.
PLoS One. 2012;7(6):e38929. doi: 10.1371/journal.pone.0038929. Epub 2012 Jun 22.
The annually reformulated trivalent inactivated influenza vaccine (TIV) includes both influenza A/subtypes (H3N2 and H1N1) but only one of two influenza B/lineages (Yamagata or Victoria). In a recent series of clinical trials to evaluate prime-boost response across influenza B/lineages, influenza-naïve infants and toddlers originally primed with two doses of 2008-09 B/Yamagata-containing TIV were assessed after two doses of B/Victoria-containing TIV administered in the subsequent 2009-10 and 2010-11 seasons. In these children, the Victoria-containing vaccines strongly recalled antibody to the initiating B/Yamagata antigen but induced only low B/Victoria antibody responses. To further evaluate this unexpected pattern of cross-lineage vaccine responses, we conducted additional immunogenicity assessment in mice. In the current study, mice were primed with two doses of 2008-09 Yamagata-containing TIV and subsequently boosted with two doses of 2010-11 Victoria-containing TIV (Group-Yam/Vic). With the same vaccines, we also assessed the reverse order of two-dose Victoria followed by two-dose Yamagata immunization (Group-Vic/Yam). The Group-Yam/Vic mice showed strong homologous responses to Yamagata antigen. However, as previously reported in children, subsequent doses of Victoria antigen substantially boosted Yamagata but induced only low antibody response to the immunizing Victoria component. The reverse order of Group-Vic/Yam mice also showed low homologous responses to Victoria but subsequent heterologous immunization with even a single dose of Yamagata antigen induced substantial boost response to both lineages. For influenza A/H3N2, homologous responses were comparably robust for the differing TIV variants and even a single follow-up dose of the heterologous strain, regardless of vaccine sequence, substantially boosted antibody to both strains. For H1N1, two doses of 2008-09 seasonal antigen significantly blunted response to two doses of the 2010-11 pandemic H1N1 antigen. Immunologic interactions between influenza viruses considered antigenically distant and in particular the cross-lineage influenza B and dominant Yamagata boost responses we have observed in both human and animal studies warrant further evaluation.
每年都会重新配制的三价灭活流感疫苗（TIV）包含两种甲型流感亚型（H3N2 和 H1N1），但只包含两种乙型流感谱系中的一种（Yamagata 或 Victoria）。在最近一系列评估流感 B 谱系间初免-加强反应的临床试验中，最初用两剂含 2008-09 年 B/Yamagata 的 TIV 进行初免的无流感史婴儿和幼儿，在随后的 2009-10 年和 2010-11 年季节中接受了两剂含 B/Victoria 的 TIV 后进行了评估。在这些儿童中，含 Victoria 的疫苗强烈回忆了针对起始 B/Yamagata 抗原的抗体，但仅诱导了低水平的 B/Victoria 抗体反应。为了进一步评估这种跨谱系疫苗反应的意外模式，我们在小鼠中进行了额外的免疫原性评估。在当前研究中，小鼠用两剂 2008-09 年含 Yamagata 的 TIV 进行初免，随后用两剂 2010-11 年含 Victoria 的 TIV 进行加强免疫（组-Yam/Vic）。用相同的疫苗，我们还评估了两剂 Victoria 随后两剂 Yamagata 免疫的相反顺序（组-Vic/Yam）。组-Yam/Vic 小鼠对 Yamagata 抗原表现出强烈的同源反应。然而，如先前在儿童中报道的那样，随后的 Victoria 抗原剂量大大增强了 Yamagata，但仅诱导了对免疫 Victoria 成分的低抗体反应。组-Vic/Yam 小鼠对 Victoria 也表现出低同源反应，但随后用即使一剂 Yamagata 抗原进行异源免疫，也会对两个谱系产生实质性的增强反应。对于甲型流感 H3N2，不同 TIV 变体的同源反应同样强劲，甚至单次后续剂量的异源株，无论疫苗序列如何，都会大大增强对两种菌株的抗体反应。对于 H1N1，两剂 2008-09 年季节性抗原显著削弱了对两剂 2010-11 年大流行 H1N1 抗原的反应。我们在人类和动物研究中观察到的流感病毒之间的免疫相互作用，被认为是抗原上的差异，特别是跨谱系的乙型流感和占主导地位的 Yamagata 增强反应，值得进一步评估。
