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Journal of Clinical and

                                                                  Translational Research



                                        REVIEW ARTICLE
                                        A systematic review of immunogenicity and

                                        safety of influenza subunit vaccines and split
                                        vaccines



                                        Lei Wang 1,2,3 , Hongbo Zhang 1,2,3 * , Dan Li 1,2,3 , Xinyue Zhang 1,2,3 , Youcai An 1,2,3 ,
                                        and Ze Chen 1,2,3 *
                                        1 Department of Basic Research, Ab &B Bio-Tech Co., Ltd., Taizhou, Jiangsu, China
                                        2 Innovative Human Vaccine Technology and Engineering Research Center of Taizhou, Taizhou,
                                        Jiangsu, China
                                        3 Innovative Antiviral Vaccines  Engineering Technology  Research  Center  of Taizhou, Taizhou,
                                        Jiangsu, China



                                        Abstract

                                        Background:  Vaccination remains the most effective preventive measure against
                                        influenza. Current flu vaccines include split-virus, subunit, and live-attenuated
                                        vaccines. Comparing adjuvanted and non-adjuvanted subunit vaccines and split-virus
                                        formulations is essential to evaluate their immunogenicity (through geometric mean
            *Corresponding authors:
            Hongbo Zhang                titers [GMTs] and seroprotection rates) and safety (adverse event rates). Aim: The aim of
            (zhanghongbo@abbbio.com.cn)   this study was to analyze the immunogenicity and safety of adjuvanted subunit vaccines,
            Ze Chen                     non-adjuvanted subunit vaccines, and split vaccines. Methods: A systematic search
            (chenze@abbbio.com.cn)
                                        of the PubMed, Cochrane, and EMBASE databases was conducted, supplemented by
            Citation: Wang L, Zhang H,   manual searches. After two reviewers independently screened the articles, extracted
            Li D, Zhang X, An Y, Chen Z.
            A systematic review of      the data, and assessed the quality, a meta-analysis was conducted with Stata 16.0
            immunogenicity and safety of   software.  Results:  Twenty-four studies were ultimately included in the analysis.
            influenza subunit vaccines and   The systematic review found that adjuvanted subunit influenza vaccines (IV), non-
            split vaccines. J Clin Transl Res.
            2025;11(3):14-37.           adjuvanted IV, and split IV all provided good protection. Based on the seroconversion
            doi: 10.36922/JCTR025060006  rate and GMTs levels, adjuvanted subunit IV was overall superior to non-adjuvanted
                                        split IV. However, adjuvanted subunit IV had lower safety compared to non-adjuvanted
            Received: February 8, 2025
                                        IV and split IV. Non-adjuvanted IV displayed similar seroprotection rates to adjuvanted
            Revised: March 15, 2025     subunit IV, providing sufficient protection. Conclusion: Adjuvanted subunit IV offers
            Accepted: April 3, 2025     better immunogenicity but has a higher incidence of adverse reactions. For individuals
                                        with impaired immune systems, it is recommended to use adjuvanted subunit  IV
            Published online: May 6, 2025
                                        for better protection. However, for the majority of the population, non-adjuvanted
            Copyright: © 2025 Author(s).   subunit IV is recommended to achieve sufficient seroprotection rates and better safety.
            This is an Open-Access article
            distributed under the terms of the   Relevance for patients: The systematic review is helpful for guiding better vaccination
            Creative Commons AttributionNon-  strategies and improves public health outcomes.
            Commercial 4.0 International (CC
            BY-NC 4.0), which permits all
            non-commercial use, distribution,   Keywords: Influenza; Adjuvant; Subunit vaccines; Split vaccines; Immunogenicity; Safety
            and reproduction in any medium,
            provided the original work is
            properly cited.
            Publisher’s Note: AccScience
            Publishing remains neutral with   1. Introduction
            regard to jurisdictional claims in
            published maps and institutional   Influenza is a respiratory infection that affects all age groups and can cause critical
            affiliations.               complications, particularly among vulnerable individuals. Due to its high contagiousness


            Volume 11 Issue 3 (2025)                        14                         doi: 10.36922/JCTR025060006
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