Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands.
Virus Reference Department, Public Health England, London, United Kingdom.
Front Immunol. 2023 Feb 22;14:1130725. doi: 10.3389/fimmu.2023.1130725. eCollection 2023.
In this short review, we summarized the results obtained with an assay to detect influenza virus-specific antibodies that mediate ADCC, which was developed and evaluated within the framework of the IMI-funded project "FLUCOP". HA-specific ADCC mediating antibodies were detected in serum samples from children and adults pre- and post-vaccination with monovalent, trivalent, or quadrivalent seasonal influenza vaccines, or following infection with H1N1pdm09 virus. Additionally, using chimeric influenza HA proteins, the presence of HA-stalk-specific ADCC mediating antibodies after vaccination and natural infection with H1N1pdm09 virus was demonstrated. With serum samples obtained from children that experienced a primary infection with an influenza B virus, we showed that primary infection induces HA-specific ADCC-mediating antibodies that cross-reacted with HA from influenza B viruses from the heterologous lineage. These cross-reactive antibodies were found to be directed to the HA stalk region. Antibodies directed to the influenza B virus HA head mediated low levels of ADCC. Finally, vaccination with a recombinant modified vaccinia virus Ankara expressing the HA gene of a clade 1 A(H5N1) highly pathogenic avian influenza virus led to the induction of ADCC-mediating antibodies, which cross-reacted with H5 viruses of antigenically distinct clades. Taken together, it is clear that virus-specific antibodies induced by infection or vaccination have immunological functionalities in addition to neutralization. These functionalities could contribute to protective immunity. The functional profiling of vaccine-induced antibodies may provide further insight into the effector functions of virus-specific antibodies and their contribution to virus-specific immunity.
在这篇简短的综述中，我们总结了在 IMI 资助的项目“FLUCOP”框架内开发和评估的检测介导 ADCC 的流感病毒特异性抗体的检测结果。在接种单价、三价或四价季节性流感疫苗之前和之后，以及在感染 H1N1pdm09 病毒之后，我们在儿童和成人的血清样本中检测到了针对 HA 的 ADCC 介导抗体。此外，使用嵌合流感 HA 蛋白，我们证明了在接种疫苗和自然感染 H1N1pdm09 病毒后，存在针对 HA 茎的 ADCC 介导抗体。使用经历了乙型流感病毒初次感染的儿童的血清样本，我们表明初次感染诱导了针对流感 B 病毒的 HA 特异性 ADCC 介导抗体，这些抗体与来自异源谱系的流感 B 病毒的 HA 发生交叉反应。这些交叉反应性抗体被发现靶向 HA 茎区。针对流感 B 病毒 HA 头部的抗体介导了低水平的 ADCC。最后，用表达具有抗原性不同的属 1 A(H5N1)高致病性禽流感病毒 HA 基因的重组改良安卡拉牛痘病毒进行疫苗接种，导致诱导了 ADCC 介导的抗体，这些抗体与抗原上不同的属 5 病毒发生交叉反应。总之，很明显，感染或接种疫苗诱导的病毒特异性抗体除了具有中和作用外，还具有免疫功能。这些功能可能有助于保护性免疫。疫苗诱导的抗体的功能分析可能为病毒特异性抗体的效应功能及其对病毒特异性免疫的贡献提供进一步的见解。
