Rajão Daniela S, Chen Hongjun, Perez Daniel R, Sandbulte Matthew R, Gauger Phillip C, Loving Crystal L, Shanks G Dennis, Vincent Amy
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, USA.
Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.
J Gen Virol. 2016 Jul;97(7):1489-1499. doi: 10.1099/jgv.0.000468. Epub 2016 Mar 31.
Multiple subtypes and many antigenic variants of influenza A virus (IAV) co-circulate in swine in the USA, complicating effective use of commercial vaccines to control disease and transmission. Whole inactivated virus (WIV) vaccines may provide partial protection against IAV with substantial antigenic drift, but have been shown to induce vaccine-associated enhanced respiratory disease (VAERD) when challenged with an antigenic variant of the same haemagglutinin (HA) subtype. This study investigated the role the immune response against HA, neuraminidase (NA) and nucleoprotein (NP) may play in VAERD by reverse engineering vaccine and challenge viruses on a common backbone and using them in a series of vaccination/challenge trials. Mismatched HA between vaccine and challenge virus was necessary to induce VAERD. However, vaccines containing a matched NA abrogated the VAERD phenomenon induced by the HA mismatch and this was correlated with NA-inhibiting (NI) antibodies. Divergence between the two circulating swine N2 lineages (92 % identity) resulted in a loss of NI cross-reactivity and also resulted in VAERD with the mismatched HA. The NP lineage selected for use in the WIV vaccine strains did not affect protection or pathology. Thus the combination of HA and NA in the vaccine virus strains played a substantial role in vaccine protection versus immunopathology, suggesting that vaccines that target the HA protein alone could be more prone to VAERD due to the absence of cross-protective NI antibodies.
甲型流感病毒（IAV）的多种亚型和许多抗原变体在美国猪群中共同传播，这使得有效使用商业疫苗来控制疾病和传播变得复杂。全灭活病毒（WIV）疫苗可能对具有显著抗原漂移的IAV提供部分保护，但已证明在受到相同血凝素（HA）亚型的抗原变体攻击时会引发疫苗相关的增强型呼吸道疾病（VAERD）。本研究通过在共同骨架上对疫苗和攻击病毒进行逆向工程，并在一系列疫苗接种/攻击试验中使用它们，研究了针对HA、神经氨酸酶（NA）和核蛋白（NP）的免疫反应在VAERD中可能发挥的作用。疫苗和攻击病毒之间不匹配的HA是诱导VAERD所必需的。然而，含有匹配NA的疫苗消除了由HA不匹配诱导的VAERD现象，这与NA抑制（NI）抗体相关。两种流行的猪N2谱系之间的差异（92%的同一性）导致NI交叉反应性丧失，也导致了与不匹配HA相关的VAERD。用于WIV疫苗株的NP谱系不影响保护或病理情况。因此，疫苗病毒株中HA和NA的组合在疫苗保护与免疫病理学方面起着重要作用，这表明仅针对HA蛋白的疫苗由于缺乏交叉保护的NI抗体可能更容易引发VAERD。
