Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, USDA, Ames, Iowa, USA.
Department of Population Health, Poultry Diagnostic and Research Center, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
J Virol. 2018 Oct 29;92(22). doi: 10.1128/JVI.01323-18. Print 2018 Nov 15.
Influenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266-8280, 2016, https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses. Due to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.
在美国流行的甲型流感病毒（IAV-S）在系统发育和抗原性上存在差异。一种人类 H3 血凝素（HA）于 20 世纪 90 年代末被引入 IAV-S 基因库，持续传播，并在 2009 年后进化成五个单系遗传分支，即 H3 分支 IV-A 到 -E。在这些系统发育分支中，确定了不同的抗原簇，其中三个簇（蓝色、红色和绿色抗原簇）是最常检测到的抗原表型之一（Abente EJ、Santos J、Lewis NS、Gauger PC、Stratton J 等人，J Virol 90：8266-8280，2016 年，https://doi.org/10.1128/JVI.01002-16）。尽管已经证明，IAV-S 的 H3N2 抗原多样性与 HA 头部几个氨基酸位置的变化有关，但这种多样性对疫苗效力的影响尚未得到测试。使用具有代表性的 H3N2 病毒，我们比较了全灭活病毒（WIV）和减毒活流感病毒（LAIV）疫苗在保护猪免受具有不同抗原性的 H3N2 病毒攻击方面的效果。WIV 对具有不同抗原性的病毒提供了部分保护，但不能防止病毒在上呼吸道复制。相比之下，LAIV 完全预防了疾病，并且在受到具有不同抗原性的病毒攻击后，未检测到病毒。由于甲型流感病毒的快速进化，疫苗需要不断更新菌株。此外，用于递送疫苗的平台也会影响保护范围。目前，有多种疫苗平台可用于预防猪流感病毒感染，我们对其中两种进行了实验测试：佐剂全灭活病毒和减毒活病毒。当受到具有不同抗原性的病毒攻击时，佐剂全灭活病毒提供了部分保护，而减毒活病毒提供了有效的保护。鉴于北美共同流行的病毒株具有动态的抗原景观，需要采取额外的策略来扩大灭活病毒疫苗的保护特性，而减毒活疫苗可能需要根据证明的交叉保护作用进行更频繁的菌株更新。提高疫苗效力以控制猪流感感染将有助于减少其对猪生产的影响，并降低猪向人类传播的风险。
