Tabynov Kairat, Kuanyshbek Aidana, Yelchibayeva Leila, Zharmambet Kuantay, Zhumadilova Zauresh, Fomin Gleb, Petrovsky Nikolai, Shekoni Olaitan C, Renukaradhya Gourapura J, Tabynov Kaissar
International Center for Vaccinology, Kazakh National Agrarian Research University, Almaty, Kazakhstan.
Central Reference Laboratory, M. Aikimbayev National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan.
Front Immunol. 2025 Mar 20;16:1539492. doi: 10.3389/fimmu.2025.1539492. eCollection 2025.
Highly pathogenic H5Nx avian influenza (HPAI) poses a significant threat to poultry health globally, necessitating the development of effective vaccination strategies.
This study assessed the immunogenicity and efficacy of a reverse-genetics-derived, Differentiating Infected from Vaccinated Animals (DIVA)-compatible inactivated H5N8 vaccine based on the IDCDC-RG71A strain. The vaccine was formulated with different adjuvants, including Montanide ISA 78 VG, ISA 71 R VG, GEL P PR, and mannose-conjugated chitosan nanoparticles, and administered via either the subcutaneous (SC) or intranasal (IN) route. To evaluate safety, the vaccine was tested in specific antibody negative (SAN) chickens, showing no adverse effects. Immunogenicity was assessed by measuring hemagglutination inhibition (HI) antibody titers, antigen-specific IgA and IgY levels, and CD4+ and CD8+ T cell proliferation. Vaccine efficacy was determined through a challenge study using a field isolate of H5N1.
This showed that a single SC dose of vaccine containing ISA 78 VG or ISA 71 R VG provided the best efficacy against infection, with high survival rates, control of abnormally high temperature incidence, reduced virus shedding, and reduced lung and liver lesions. The ISA 78 VG-adjuvanted SC vaccine induced the highest HI titers and CD4+ T cell proliferation, while ISA 71 R VG and GEL P PR elicited the strongest IgY responses. In contrast, IN formulations induced IgA in the lungs and trachea however, even after two doses, failed to generate high HI titers and provided poor, if any, protection against infection. This highlights the superior efficacy of the SC over the IN route of vaccination for reducing H5N1 viral shedding.
These results underscore the importance of both the adjuvants and delivery route to maximize HPAI vaccine efficacy. This presented system could thereby be used to develop potent and DIVA-compatible vaccines to enhance biosecurity and disease management in regions affected by endemic HPAI.
高致病性H5Nx禽流感（HPAI）对全球家禽健康构成重大威胁，因此需要制定有效的疫苗接种策略。
本研究评估了一种基于IDCDC-RG71A毒株的反向遗传学衍生的、可区分感染动物与疫苗接种动物（DIVA）的H5N8灭活疫苗的免疫原性和效力。该疫苗与不同佐剂一起配制，包括Montanide ISA 78 VG、ISA 71 R VG、GEL P PR和甘露糖共轭壳聚糖纳米颗粒，并通过皮下（SC）或鼻内（IN）途径给药。为评估安全性，该疫苗在特定抗体阴性（SAN）鸡中进行了测试，未显示出不良反应。通过测量血凝抑制（HI）抗体滴度、抗原特异性IgA和IgY水平以及CD4+和CD8+T细胞增殖来评估免疫原性。通过使用H5N1田间分离株进行攻毒试验来确定疫苗效力。
结果表明，单剂量皮下接种含ISA 78 VG或ISA 71 R VG的疫苗对感染具有最佳效力，具有高存活率、控制异常高温发生率、减少病毒脱落以及减少肺和肝损伤。含ISA 78 VG佐剂的皮下疫苗诱导了最高的HI滴度和CD4+T细胞增殖，而ISA 71 R VG和GEL P PR引发了最强的IgY反应。相比之下，鼻内制剂在肺和气管中诱导了IgA，然而，即使接种两剂后，也未能产生高HI滴度，并且对感染的保护作用很差（如果有保护作用的话）。这突出了皮下接种途径在减少H5N1病毒脱落方面优于鼻内接种途径。
这些结果强调了佐剂和给药途径对于最大化HPAI疫苗效力的重要性。因此，该系统可用于开发有效的、与DIVA兼容的疫苗，以加强受地方性HPAI影响地区的生物安全和疾病管理。
