Desheva Yulia, Mayorova Irina, Rekstin Andrey, Sokolovsky Daniil, Kudar Polina, Kopylova Nina, Guzenkov Danila, Petrachkova Darya, Mamontov Andrey, Trullioff Andrey, Kiseleva Irina
Federal State Budgetary Scientific Institution "Institute of Experimental Medicine", 197022 St. Petersburg, Russia.
Medical Institute, St. Petersburg State University, 199034 St. Petersburg, Russia.
Vaccines (Basel). 2025 Sep 11;13(9):966. doi: 10.3390/vaccines13090966.
BACKGROUND/OBJECTIVES: Antigenic drift of influenza A(H1N1pdm09) viruses has led to periodic replacement of vaccine strains. Understanding how structural differences in glycoproteins influence immune protection is crucial for improving vaccine effectiveness.
We conducted a structural analysis of the hemagglutinin (HA) and neuraminidase (NA) glycoproteins from drifted A(H1N1)pdm09 strains: A/South Africa/3626/2008 and A/Guangdong-Maonan/SWL1/2020, as well as their cold-adapted live attenuated vaccine (LAIV) reassortant strains (A/17/South Africa/2013/01(H1N1)pdm09 and A/17/Guangdong-Maonan/2019/211(H1N1)pdm09). We compared their replication in chicken embryo and mammalian cell culture, assessed type I interferon induction, and evaluated post-vaccine protection in mice after homologous and heterogeneous viral challenges.
The two vaccine strains had distinct glycosylation patterns for HA and NA. However, they had similar replication capacity in embryonated egg and mammalian cells. In the mouse respiratory tract, both strains replicated similarly. A/17/South Africa/2013/01(H1N1)pdm09 induced significantly higher levels of IFN-α and Mx1 in vitro, and it elicited earlier IgM and IgG response after vaccination in mice. At day 6 after immunization, it provided 70% protection from homologous challenge. A/17/Guangdong-Maonan/2019/211(H1N1)pdm09 did not prevent death, but it reduced viral titer in the lungs. Interestingly, A/17/South Africa/2013/01(H1N1)pdm09 provided full protection from heterologous H5N1 challenge, while A/17/Guangdong-Maonan/2019/211(H1N1)pdm09) only provided partial protection.
Differences in HA and NA glycans among A(H1N1)pdm09 strains may influence innate and adaptive immunity, as well as cross-protection. These findings emphasize the importance of glycoprotein structure when selecting vaccine candidates for optimal homologous and cross-protection against influenza.
背景/目的：甲型H1N1pdm09流感病毒的抗原漂移导致疫苗株的定期更换。了解糖蛋白的结构差异如何影响免疫保护对于提高疫苗效力至关重要。
我们对发生抗原漂移的甲型H1N1pdm09毒株（A/南非/3626/2008和A/广东茂名/SWL1/2020）及其冷适应减毒活疫苗（LAIV）重配毒株（A/17/南非/2013/01(H1N1)pdm09和A/17/广东茂名/2019/211(H1N1)pdm09）的血凝素（HA）和神经氨酸酶（NA）糖蛋白进行了结构分析。我们比较了它们在鸡胚和哺乳动物细胞培养中的复制情况，评估了I型干扰素的诱导情况，并在同源和异源病毒攻击后评估了小鼠接种疫苗后的保护作用。
两种疫苗株的HA和NA具有不同的糖基化模式。然而，它们在胚胎蛋和哺乳动物细胞中的复制能力相似。在小鼠呼吸道中，两种毒株的复制情况相似。A/17/南非/2013/01(H1N1)pdm09在体外诱导的IFN-α和Mx1水平显著更高，并且在小鼠接种疫苗后引发了更早的IgM和IgG反应。免疫后第6天，它对同源攻击提供了70%的保护。A/17/广东茂名/2019/211(H1N1)pdm09不能预防死亡，但它降低了肺部的病毒滴度。有趣的是，A/17/南非/2013/01(H1N1)pdm09对异源H5N1攻击提供了完全保护，而A/17/广东茂名/2019/211(H1N1)pdm09只提供了部分保护。
甲型H1N1pdm09毒株之间HA和NA聚糖的差异可能影响先天性和适应性免疫以及交叉保护。这些发现强调了在选择疫苗候选株以实现针对流感的最佳同源和交叉保护时糖蛋白结构的重要性。
