A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response
A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response
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DOI：
10.1093/infdis/jiu123
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发表时间：
2014-06-15
影响因子：
6.4
通讯作者：
Subbarao, Kanta
中科院分区：
文献类型：
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作者：
Talaat, Kawsar R.;Luke, Catherine J.;Subbarao, Kanta
背景。高致病性甲型禽流感（H5N1）会导致人类严重感染。我们生产了 2 种用于大流行的甲型 (H5N1) 流感减毒活疫苗 (pLAIV)，但它们未能引发初级免疫反应。我们的目的是确定疫苗是否引发或建立了持久的免疫力，这种免疫力可以通过施用灭活亚病毒粒子甲型流感 (H5N1) 疫苗 (ISIV) 来检测。方法。以下人群被邀请参加该研究： 曾经接受过甲型流感（H5N1） pLAIV 的人；以前接受过不相关的甲型H7N3流感pLAIV的人；以及曾感染过甲型 H5N1 流感和 LAIV 的社区成员。经历过 LAIV 的受试者接受单剂量 45 微克甲型流感 (H5N1) ISIV。甲型流感 (H5N1) 和 LAIV 初治受试者接受 1 或 2 剂 ISIV。结果。与那些未接触过甲型（H5N1）流感和 LAIV 并接受 2 剂 ISIV 的受试者相比，在先前接受过抗原匹配的甲型（H5N1）流感 pLAIV 随后接受 1 剂 ISIV 的受试者中，我们观察到抗体反应频率增加（82% vs 50%，通过血凝抑制测定）和显着更高的抗体滴度（112 vs 76；P = 0.04）。在甲型流感 (H5N1) pLAIV 引发的受试者中，抗体的亲和力和跨进化枝中和的广度也得到增强。结论。 ISIV 给药揭示了甲型流感 (H5N1) pLAIV 接受者的持久免疫力，具有快速、高滴度、高质量的抗体反应，该反应在多个甲型流感 (H5N1) 进化枝之间广泛交叉反应。
Background. Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV).Methods. The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-mu g dose of influenza A(H5N1) ISIV. Influenza A(H5N1)- and LAIV-naive subjects received either 1 or 2 doses of ISIV.Results. In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P =.04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV-primed subjects.Conclusions. ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades.