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REVIEW ARTICLE

A systematic review of immunogenicity and safety of influenza subunit vaccines and split vaccines

Lei Wang1,2,3 ,  Hongbo Zhang1,2,3* ,  Dan Li1,2,3 ,  Xinyue Zhang1,2,3 ,  Youcai An1,2,3 ,  Ze Chen1,2,3*
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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
JCTR, 025060006 https://doi.org/10.36922/JCTR025060006
Received: 8 February 2025 | Revised: 15 March 2025 | Accepted: 3 April 2025 | Published online: 6 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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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 titers [GMTs] and seroprotection rates) and safety (adverse event rates). Aim: The aim of this study was to analyze the immunogenicity and safety of adjuvanted subunit vaccines, non-adjuvanted subunit vaccines, and split vaccines. Methods: A systematic search of the PubMed, Cochrane, and EMBASE databases was conducted, supplemented by manual searches. After two reviewers independently screened the articles, extracted the data, and assessed the quality, a meta-analysis was conducted with Stata 16.0 software. Results: Twenty-four studies were ultimately included in the analysis. The systematic review found that adjuvanted subunit influenza vaccines (IV), non-adjuvanted IV, and split IV all provided good protection. Based on the seroconversion 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 IV and split IV. Non-adjuvanted IV displayed similar seroprotection rates to adjuvanted subunit IV, providing sufficient protection. Conclusion: Adjuvanted subunit IV offers better immunogenicity but has a higher incidence of adverse reactions. For individuals with impaired immune systems, it is recommended to use adjuvanted subunit IV for better protection. However, for the majority of the population, non-adjuvanted subunit IV is recommended to achieve sufficient seroprotection rates and better safety. Relevance for patients: The systematic review is helpful for guiding better vaccination strategies and improves public health outcomes.

Keywords
Influenza
Adjuvant
Subunit vaccines
Split vaccines
Immunogenicity
Safety
Funding
This work was supported by the Fengcheng Talents Plan, a part of the 113 Biomedical Special Grant of Taizhou, China.
Conflict of interest
All authors declare that they have no conflicts of interest.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing
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