Hu Zenglei, Jiao Xinan, Liu Xiufan
Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Front Microbiol. 2017 Sep 26;8:1898. doi: 10.3389/fmicb.2017.01898. eCollection 2017.
Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their seasonal counterparts. A large fraction of overall IgG antibody is non-neutralizing antibody and they target unrecognized epitopes outside of the traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA may at least partially contribute to regulation of antibody immunity. Here, we review the latest advances for the development of H7N9 vaccines and discuss the influence of serological criteria on evaluation of immunogenicity of H7N9 vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9 vaccines, including the change in antigenic epitopes in HA and the presence of the Treg epitope. Last, we present our perspectives for the unique features of antibody immunity of H7N9 vaccines and propose some future directions to improve or modify antibody response induced by H7N9 vaccines. This perspective would provide critical implications for rational design of H7N9 vaccines for human and veterinary use.
人类感染H7N9高致病性禽流感病毒（AIV），使世界各地的公共卫生当局对可能出现的人流感大流行保持高度警惕。目前，新出现的高致病性甲型H7N9禽流感病毒对公共卫生和家禽业构成了双重挑战。利用各种平台已研发出众多H7N9候选疫苗。在动物和人体上进行的免疫试验表明，H7N9疫苗的免疫原性明显较差，因为它们诱导产生的血凝抑制和病毒中和抗体效价较低。然而，H7N9疫苗诱导产生的血凝素（HA）反应性IgG抗体总量水平与季节性流感疫苗相当，这表明H7N9疫苗的免疫原性与其季节性同类疫苗相同。总体IgG抗体中的很大一部分是非中和抗体，它们靶向HA中传统抗原位点之外未被识别出的表位。此外，在H7 HA中鉴定出的调节性T细胞（Treg）表位可能至少部分有助于调节抗体免疫。在此，我们综述了H7N9疫苗研发的最新进展，并讨论了血清学标准对H7N9疫苗免疫原性评估的影响。接下来，我们讨论影响H7N9疫苗诱导抗体免疫的因素，包括HA中抗原表位的变化以及Treg表位的存在。最后，我们阐述了对H7N9疫苗抗体免疫独特特征的看法，并提出了一些未来改进或调整H7N9疫苗诱导抗体反应的方向。这一观点将为合理设计用于人类和兽医的H7N9疫苗提供关键启示。
