EBioMedicine
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2022
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IF 11.205
Mengyi Zhang,Yimeng An,Xi Wu,Meina Cai,Xinyu Zhang,Chaoying Yang,Jincheng Tong,Zhimin Cui,Xueli Li,Weijin Huang,Chenyan Zhao,Youchun Wang
Summary Background Influenza A (H3N2) virus (A/H3N2) has complex antigenic evolution, resulting in frequent vaccine strain updates. We aimed to evaluate the protective effect of the vaccine strains on the circulating strains from past ten years and provide a basis for finding a broader and more efficient A/H3N2 vaccine strain. Methods Eighty-four representative circulating A/H3N2 strains were selected from 65,791 deposited sequences in 2011–2020 and pseudotyped viruses were constructed with the VSV vector. We immunized guinea pigs with DNA vaccine containing the A/H3N2 components of the vaccine strains from 2011 to 2021 and tested neutralizing antibody against the pseudotyped viruses. We used a hierarchical clustering method to classify the eighty-four representative strains into different antigenic clusters. We also immunized animals with monovalent vaccine stock of the vaccine strains for the 2020–2021 and 2021–2022 seasons and tested neutralizing antibody against the pseudotyped viruses. Findings The vaccine strains PE/09, VI/11 and TE/12 induced higher levels of neutralizing antibody against representative strains circulating in recommended year and the year immediately prior whereas vaccine strains HK/14, HK/19 and CA/20 induced poor neutralization against all representative strains. The representative strains were divided into five antigenic clusters (AgV), which were not identical to gene clades. The AgV5 strains were most difficult to be protected among the five clusters. Compared with single-dose immunization, three doses of monovalent vaccine stock (HK/19 or CA/20) could induce stronger and broader neutralizing antibodies against strains in each of the antigenic clusters. Interpretation The protective effect of vaccine strains indicated that the accurate selection of A/H3N2 vaccine strains must remain a top priority. By increasing the frequency of immunization, stronger and broader neutralizing antibodies against strains in all antigenic clusters were induced, which provides direction for a new immunization strategy. Funding This work was supported by a grant from National Key R&D Program of China (No. 2021YFC2301700 ).
研究领域:
病毒学
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免疫学
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流行病学
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DOI
PubMed
高影响因子
Human Vaccines & Immunotherapeutics
·
2024
·
IF 4.1
Xiande Huang,Ziqi Cheng,Yake Lv,Weixuan Li,Xiaoyu Liu,Weijin Huang,Chenyan Zhao
Seasonal influenza is a severe disease that significantly impacts public health, causing millions of infections and hundreds of thousands of deaths each year. Seasonal influenza viruses, particularly the H3N2 subtype, exhibit high antigenic variability, often leading to mismatch between vaccine strains and circulating strains. Therefore, rapidly assessing the alignment between existing seasonal influenza vaccine and circulating strains is crucial for enhancing vaccine efficacy. This study, based on a pseudovirus platform, evaluated the match between current influenza H3N2 vaccine strains and circulating strains through cross-neutralization assays using clinical human immune sera against globally circulating influenza virus strains. The research results show that although mutations are present in the circulating strains, the current H3N2 vaccine strain still imparting effective protection, providing a scientific basis for encouraging influenza vaccination. This research methodology can be sustainably applied for the neutralization potency assessment of subsequent circulating strains, establishing a persistent methodological framework.
研究领域:
病毒学
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流行病学
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公共卫生
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DOI
高影响因子
Emerging Microbes & Infections
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2026
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IF 7
Yimeng An,Meina Cai,Chenyan Zhao,Mengyi Zhang,Xi Wu,Weijin Huang,Xu Zhou,Youchun Wang
Seasonal influenza A/H3N2 poses a significant public health burden due to its rapid antigenic evolution, necessitating frequent vaccine updates. This study systematically analysed the antigenic evolution of 14 H3N2 vaccine strains (2000–2022) using pseudovirus-based neutralization assays and antigenic cartography. Vaccine strains exhibited cross-neutralization patterns, with higher reactivity among strains from adjacent years, forming six antigenic clusters. Key amino acid mutations (e.g. 144K, 189N) were identified as critical drivers of antigenic variation, with clustering-specific effects on neutralization sensitivity. Based on these findings, a consensus HA immunogen (consensus up-HA) was designed by combining mutations at key sites. This immunogen demonstrated broad-spectrum neutralization against pseudoviruses representing circulating strains from 2011 to 2024, including recent variants. These results highlight the potential of targeted HA modifications to develop broadly cross-reactive H3N2 vaccine candidate, offering broader and more durable neutralizing activity against evolving H3N2 strains.
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DOI
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
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2018
·Vol. 233
·期 12
·9763-9776
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IF 3.923
Xing Xie,Yuan Gan,Maoda Pang,Guoqing Shao,Lei Zhang,Beibei Liu,Qi Xu,Haiyan Wang,Yanyan Feng,Yanfei Yu,Rong Chen,Meng Wu,Zhenzhen Zhang,Lizhong Hua,Qiyan Xiong,Maojun Liu,Zhixin Feng
Primary porcine bronchial epithelial cells (PBECs) are an ideal model to study the molecular and pathogenic mechanisms of various porcine respiratory pathogens. However, the short lifespan of primary PBECs greatly limit their application. Here, we isolated and cultured primary PBECs and established immortalized PBECs by transfecting primary PBECs with the pEGFP-hTERT recombinant plasmid containing human telomerase reverse transcriptase (hTERT). Immortalized PBECs (hTERT-PBECs) retained the morphological and functional features of primary PBECs as indicated by cytokeratin 18 expression, telomerase activity assay, proliferation assays, karyotype analysis, and quantitative reverse-transcriptase polymerase chain reaction. Compared to primary PBECs, hTERT-PBECs had higher telomerase activity, extended replicative lifespan, and displayed enhanced proliferative activity. Moreover, this cell line is not transformed in vitro and does not exhibit a malignant phenotype in vivo, suggesting that it can be safely used in further studies. Besides, hTERT-PBECs were susceptible to swine influenza virus of H3N2 subtype and porcine circovirus type 2. In conclusion, the immortalized hTERT-PBECs represent a valuable in vitro model, which can be widely used in the study of porcine respiratory pathogenic infections.
研究领域:
细胞生物学
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病毒学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）