Journal of Vaccine Research 2024, Vol.14, No.6, 297-306 http://medscipublisher.com/index.php/jvr 297 Feature Review Open Access The Role of T-cell Responses in Universal Influenza Vaccine Efficacy Jianhui Li Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, China Corresponding author email: jianhui.li@jicat.org Journal of Vaccine Research, 2024, Vol.14, No.6 doi: 10.5376/jvr.2024.14.0028 Received: 01 Oct., 2024 Accepted: 11 Nov., 2024 Published: 05 Dec., 2024 Copyright © 2024 Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Preferred citation for this article: Li J.H., 2024, The role of T-cell responses in universal influenza vaccine efficacy, Journal of Vaccine Research, 14(6): 297-306 (doi: 10.5376/jvr.2024.14.0028) Abstract This study reveals the important role of T-cell immunity in the development of universal influenza vaccines. Unlike traditional vaccines that rely on antibodies, T-cell vaccines can act on the conacted regions of the virus, thereby providing extensive and long-lasting protection against multiple influenza strains. Experimental data indicate that CD4+ and CD8+ T cells, especially memory T cells and TRM cells residing in respiratory tract tissues, play a key role in inhibiting viral infection and alleviating symptoms. These TRM cells can rapidly initiate protective immune responses when the virus invades again. Future vaccine research and development should focus on verifying the clinical protective effect of T cells, optimizing the induction strategy of respiratory tract TRM cells, and combining T cell immunity with antibody technology. This innovative direction is expected to significantly enhance the ability to prevent and control influenza and provide long-term immune protection against the constantly mutating virus. Keywords T-cell responses; Universal influenza vaccine; Memory T-cells; Cross-protection; Immune escape 1 Introduction Influenza A virus (IAV) remains a significant challenge to global public health. Its rapid mutation characteristics resulting from antigen drift and transformation have continuously hindered vaccine development (Sridhar, 2016; Grant et al., 2016). Current vaccines mainly target mutatable surface proteins, but the emergence of new strains often significantly weakens the protective effect (Valkenburg et al., 2018; Schmidt and Lapuente, 2021), which highlights the urgency of innovating vaccine strategies. The current immunization regimens overly rely on the antibody response mechanism, and there is significant room for improvement. The ideal vaccine should have cross-strain protection ability and be able to maintain efficacy even in the face of major mutations (Sridhar, 2016; Clemens et al., 2018). Vaccine strategies based on T cells show breakthrough potential: Such vaccines target the stable regions of the virus and can recognize multiple subtypes (Savic et al., 2016; Schmidt and Lapuente, 2021), which can not only break through the strain matching limit but also establish long-term defense (Valkenburg et al., 2018; Moraes et al., 2023). This study focuses on analyzing the core role of T-cell immunity in universal vaccines and emphasizes the exploration of how CD4+/CD8+ T cells (especially tissue-resident memory cells) achieve cross-immune protection. The relevant findings will guide the development of new vaccines with broad-spectrum and long-lasting protective efficacy, providing key technical support for responding to influenza pandemics. 2 Influenza Virus and the Basis of T-cell Immunity 2.1 Virus characteristics and antigen evolution The surface of the influenza virus mainly carries two glycoproteins, hemagglutinin (HA) and neuraminidase (NA). These proteins achieve immune escape through continuous genetic variations (antigen drift). Studies have shown that the spherical head of HA protein, as the main action site of antibodies, shows high variability, while its stem region and some structures of NA protein are relatively conserved (Basha et al., 2011a; Basha et al., 2011b). This stability makes them important targets for the development of broad-spectrum vaccines (Andrews et al., 2018; Zost et al., 2019).
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