Journal of Vaccine Research 2024, Vol.14, No.2, 40-53 http://medscipublisher.com/index.php/jvr 40 Systematic Review Open Access Universal Influenza Vaccines: Mechanisms of Broad Protection Jianhui Li Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, China Corresponding email: jianhui.li@jicat.org Journal of Vaccine Research, 2024, Vol.14, No.2 doi: 10.5376/jvr.2024.14.0006 Received: 01 Mar., 2024 Accepted: 02 Apr., 2024 Published: 15 Apr., 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 adjuvants in cancer vaccine development, Journal of Vaccine Research, 14(2): 40-53 (doi: 10.5376/jvr.2024.14.0006) Abstract The effectiveness of seasonal influenza vaccines varies with changes in virus strains, posing challenges for controlling influenza outbreaks. In recent years, the development of a universal influenza vaccine (UIV) capable of providing broad protection has become a focal point in influenza research. This study explores the potential mechanisms by which a universal influenza vaccine can achieve broad protection, including targeting conserved antigens, inducing broadly neutralizing antibodies (bnAbs), activating T-cell responses, and innate immune responses. By reviewing existing literature and clinical trial data, the study analyzes the key mechanisms in the development of universal influenza vaccines, such as targeting the hemagglutinin (HA) stem domain, neuraminidase, and M2 protein, as well as the role of broadly neutralizing antibodies and T-cell responses. The research indicates that vaccine strategies targeting conserved antigens and broadly neutralizing antibodies show significant broad protective effects in animal models. Additionally, T-cell-mediated immune responses also play a crucial role in preventing influenza infection. The successful development of a universal influenza vaccine would eliminate the dependency on strain-specific vaccines, provide long-term and effective protection against multiple influenza strains, significantly reduce influenza morbidity and mortality, alleviate the burden on healthcare systems, and have a profound impact on global public health security. Keywords Universal influenza vaccine; Broadly neutralizing antibodies; T-cell response; Conserved antigens; Broad protection mechanisms 1 Introduction Influenza viruses are significant respiratory pathogens that pose a substantial public health burden worldwide, causing up to 650,000 deaths annually (Freyn et al., 2020). These viruses are responsible for seasonal epidemics and occasional pandemics, leading to widespread morbidity and mortality (Vogel and Manicassamy, 2020). The constant evolution of influenza viruses through antigenic drift and shift complicates the control and prevention of influenza outbreaks (Nachbagauer et al., 2021). Current seasonal influenza vaccines primarily target the highly variable hemagglutinin (HA) and neuraminidase (NA) proteins of the virus, necessitating annual reformulation to match the predicted circulating strains (Nabel and Fauci, 2010; Lo et al., 2021). This approach has several limitations, including imperfect strain prediction, lengthy vaccine production times, and variable vaccine efficacy (Pica and Palese, 2013; Memoli et al., 2020). Additionally, the emergence of unexpected pandemic strains further challenges the effectiveness of seasonal vaccines (Pica and Palese, 2013). Given the limitations of seasonal vaccines, there is a critical need for universal influenza vaccines (UIVs) that provide broad and durable protection against diverse influenza virus strains (Jang and Seong, 2019; Vogel and Manicassamy, 2020). UIVs aim to target conserved viral antigens, such as the HA stalk, matrix 2 (M2) protein, and nucleoprotein (NP), to elicit long-lasting immune responses that are effective against multiple influenza subtypes (Krammer et al., 2013; Freyn et al., 2020; Lo et al., 2021). The development of UIVs is a priority in influenza research, as they have the potential to eliminate the need for annual vaccine updates and improve pandemic preparedness (Vogel and Manicassamy, 2020). This study explores the mechanisms by which universal influenza vaccines (UIVs) provide broad protection. By reviewing the latest advancements in UIV research, including new vaccine designs and immunization strategies,
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