Zhang Ao, Tan Bin, Wang Jiahui, Zhang Shuqin
Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
Vaccines (Basel). 2025 Jul 23;13(8):783. doi: 10.3390/vaccines13080783.
: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza vaccine development. NA has potential advantages as a vaccine antigen in providing cross-protection, with specific antibodies that have a broad binding capacity for heterologous viruses. In this study, we evaluated the immunogenicity and protective efficacy of a tetrameric recombinant NA subunit vaccine in a swine model. : We constructed and expressed structurally stable soluble tetrameric recombinant NA (rNA) and prepared subunit vaccines by mixing with ISA 201 VG adjuvant. The protective efficacy of rNA-ISA 201 VG was compared to that of a commercial whole inactivated virus vaccine. Pigs received a prime-boost immunization (14-day interval) followed by homologous viral challenge 14 days post-boost. : Both rNA-ISA 201 VG and commercial vaccine stimulated robust humoral responses. Notably, the commercial vaccine group exhibited high viral-binding antibody titers but very weak NA-specific antibodies, whereas rNA-ISA 201 VG immunization elicited high NA-specific antibody titers alongside substantial viral-binding antibodies. Post-challenge, both immunization with rNA-ISA 201 VG and the commercial vaccine were effective in inhibiting viral replication, reducing viral load in porcine respiratory tissues, and effectively mitigating virus-induced histopathological damage, as compared to the PBS negative control. : These findings found that the anti-NA immune response generated by rNA-ISA 201 VG vaccination provided protection comparable to that of a commercial inactivated vaccine that primarily induces an anti-HA response. Given that the data are derived from one pig per group, there is a requisite to increase the sample size for more in-depth validation. This work establishes a novel strategy for developing next-generation SIV subunit vaccines leveraging NA as a key immunogen.
甲型猪流感病毒（swIAV）是猪群中一种普遍存在的呼吸道病原体，给全球畜牧业带来了巨大的经济损失，并对公共卫生安全构成潜在威胁。神经氨酸酶（NA）已被提议作为通用流感疫苗开发的重要组成部分。NA作为疫苗抗原具有潜在优势，可提供交叉保护，其特异性抗体对异源病毒具有广泛的结合能力。在本研究中，我们在猪模型中评估了四聚体重组NA亚单位疫苗的免疫原性和保护效果。
我们构建并表达了结构稳定的可溶性四聚体重组NA（rNA），并通过与ISA 201 VG佐剂混合制备了亚单位疫苗。将rNA-ISA 201 VG的保护效果与市售全病毒灭活疫苗进行了比较。猪接受了初次加强免疫（间隔14天），然后在加强免疫后14天进行同源病毒攻击。
rNA-ISA 201 VG和市售疫苗均刺激了强烈的体液反应。值得注意的是，市售疫苗组表现出高病毒结合抗体滴度，但NA特异性抗体非常弱，而rNA-ISA 201 VG免疫诱导了高NA特异性抗体滴度以及大量病毒结合抗体。攻击后，与PBS阴性对照相比，rNA-ISA 201 VG免疫和市售疫苗均能有效抑制病毒复制，降低猪呼吸道组织中的病毒载量，并有效减轻病毒诱导的组织病理学损伤。
这些发现表明，rNA-ISA 201 VG疫苗接种产生的抗NA免疫反应提供的保护与主要诱导抗HA反应的市售灭活疫苗相当。鉴于数据来自每组一头猪，有必要增加样本量以进行更深入的验证。这项工作建立了一种利用NA作为关键免疫原开发下一代SIV亚单位疫苗的新策略。
