Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Wuhan Institute of Biological Products Co. Ltd., Wuhan, China.
J Med Virol. 2024 Oct;96(10):e29858. doi: 10.1002/jmv.29858.
The COVID-19 pandemic had a significant impact on the global influenza vaccination and the epidemics of seasonal influenza. To further explore the molecular epidemiology of influenza viruses and assess vaccine effectiveness, we collected influenza cases in Wuhan during the 2022-2023 influenza season. Among 1312 clinical samples, 312 samples tested positive for influenza viruses using reverse transcription polymerase chain reaction. These positive samples included 146A/H1N1 subtypes (46.8%), 164A/H3N2 subtypes (52.6%) and 2 influenza B virus types (0.6%). Based on the whole genome sequence information of hemagglutinin (HA) and neuraminidase (NA) from 27A/H1N1 influenza virus strains and 26A/H3N2 influenza virus strains obtained in this study, a phylogenetic analysis was conducted. The analysis revealed that all A/H1N1 strains belonged to the evolutionary branch 6B.1A.5a.2a, and they exhibited specific substitutions at positions K71Q, Q206E, E241A, and R276K. Similarly, all A/H3N2 strains were classified into the 3C.2a1b.2a.1a subclade and displayed amino acid substitutions at positions S172H, N175Y, I176T, K187N, and S214P. Notably, the A/H3N2 strains also acquired a new potential glycosylation site at position N174. Using an epitope model, the predicted vaccine effectiveness was assessed for the A/H1N1 and A/H3N2 strains. The predicted vaccine effectiveness against the Wuhan influenza epidemic strain was over 85% for the A/H1N1 vaccine strain. However, the effectiveness against the A/H3N2 vaccine strain was only 48.7%. To further verify the protection of influenza vaccine against circulating influenza viruses in the region, we conducted in vivo and in vitro animal studies. The results of in vitro neutralization experiment showed that rabbit serum antibodies inoculated with quadrivalent isolated influenza vaccine had neutralization ability against all 24 isolated influenza viruses. In vivo experiments showed that vaccinated mice had fewer lung lesions when infected with the influenza strain circulating in Wuhan, suggesting that vaccination can effectively reduce the occurrence of severe lung damage. These findings emphasize the importance of accurately predicting seasonal influenza strains for effective influenza prevention and control, especially during the co-circulation of SARS-CoV-2 and influenza viruses. This study provides valuable information on the seasonal influenza virus in Wuhan during the COVID-19 pandemic and serves as a basis for vaccine prediction and updates.
新冠疫情对全球流感疫苗接种和季节性流感流行产生了重大影响。为了进一步探讨流感病毒的分子流行病学并评估疫苗的有效性，我们收集了 2022-2023 年武汉流感季节的流感病例。在 1312 份临床样本中，通过逆转录聚合酶链反应（RT-PCR）检测到 312 份样本流感病毒呈阳性。这些阳性样本包括 146A/H1N1 亚型（46.8%）、164A/H3N2 亚型（52.6%）和 2 种流感 B 病毒类型（0.6%）。基于本研究中获得的 27 株 A/H1N1 流感病毒株和 26 株 A/H3N2 流感病毒株血凝素（HA）和神经氨酸酶（NA）的全基因组序列信息，进行了系统进化分析。分析表明，所有 A/H1N1 株均属于进化枝 6B.1A.5a.2a，在位置 K71Q、Q206E、E241A 和 R276K 处具有特定的取代。同样，所有 A/H3N2 株均归类为 3C.2a1b.2a.1a 亚分支，在位置 S172H、N175Y、I176T、K187N 和 S214P 处具有氨基酸取代。值得注意的是，A/H3N2 株还在位置 N174 处获得了一个新的潜在糖基化位点。使用表位模型评估了 A/H1N1 和 A/H3N2 株的预测疫苗有效性。针对 A/H1N1 疫苗株，针对武汉流感流行株的预测疫苗有效性超过 85%。然而，针对 A/H3N2 疫苗株的有效性仅为 48.7%。为了进一步验证流感疫苗对该地区流行流感病毒的保护作用，我们进行了体内和体外动物研究。体外中和实验结果表明，接种四价分离流感疫苗的兔血清抗体对所有 24 株分离流感病毒均具有中和能力。体内实验表明，接种疫苗的小鼠在感染武汉流行的流感株时肺部病变较少，提示疫苗接种可有效减少严重肺部损伤的发生。这些发现强调了准确预测季节性流感株对于有效流感预防和控制的重要性，尤其是在 SARS-CoV-2 和流感病毒共同流行期间。本研究为武汉季节性流感病毒提供了有价值的信息，为疫苗预测和更新提供了依据。
