Retrospective immunogenicity analysis of seasonal flu H3N2 vaccines recommended in the past ten years using immunized animal seraResearch in context
Mengyi Zhang,
Yimeng An,
Xi Wu,
Meina Cai,
Xinyu Zhang,
Chaoying Yang,
Jincheng Tong,
Zhimin Cui,
Xueli Li,
Weijin Huang,
Chenyan Zhao,
Youchun Wang
Affiliations
Mengyi Zhang
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Yimeng An
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China; Shanghai Institute of Biological Products Co. LTD, 350 Anshun Road, Changning District, Shanghai, 200051, China
Xi Wu
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Meina Cai
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China; Graduate School of Peking Union Medical College, No. 9 Dongdan Santiao, Dongcheng District, Beijing, 100730, China
Xinyu Zhang
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Chaoying Yang
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Jincheng Tong
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Zhimin Cui
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Xueli Li
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China
Weijin Huang
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China; Corresponding author.
Chenyan Zhao
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China; Corresponding author.
Youchun Wang
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China; Graduate School of Peking Union Medical College, No. 9 Dongdan Santiao, Dongcheng District, Beijing, 100730, China; Changping Laboratory, Yard 28, Science Park Road, Changping District, Beijing; Corresponding author. Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China.
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).
