Journal of Vaccine Research 2024, Vol.14, No.4, 157-169 http://medscipublisher.com/index.php/jvr 157 Systematic Review Open Access Strategies for Antigen Design in Universal Influenza Vaccine Development Jianbang Chen Huahai Pharmaceutical Co., Ltd., Taizhou, 317099, Zhejiang, China Corresponding email: chejb@qq.com Journal of Vaccine Research, 2024, Vol.14, No.4 doi: 10.5376/jvr.2024.14.0016 Received: 10 Jun., 2024 Accepted: 11 Jul., 2024 Published: 22 Jul., 2024 Copyright © 2024 Chen, 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: Chen J.B., 2024, Strategies for antigen design in universal influenza vaccine development, Journal of Vaccine Research, 14(4): 157-169 (doi: 10.5376/jvr.2024.14.0016) Abstract Globally, the variability and antigenic drift of the influenza virus limit the effectiveness of existing seasonal vaccines, making the development of a universal influenza vaccine that provides broad and durable protection critically important. This study reviews the primary strategies for designing antigens for a universal influenza vaccine, focusing on innovative approaches targeting conserved regions of the influenza virus, such as the hemagglutinin (HA) stem, neuraminidase (NA), and matrix protein 2 (M2). It also explores the roles of chemical synthesis, nanoparticle carriers, and novel adjuvants in enhancing antigen immunogenicity. By analyzing current clinical and preclinical research findings, the study identifies key challenges related to antigen immunodominance, infection enhancement, and long-term efficacy and durability. The research concludes with an outlook on future research directions and calls for further scientific exploration to achieve the ultimate goal of a universal influenza vaccine. Keywords Universal influenza vaccine; Antigen design; Hemagglutinin stem; Matrix protein 2 1 Introduction The pursuit of a universal influenza vaccine has garnered significant attention due to the persistent challenge posed by influenza viruses, which undergo frequent antigenic shifts and drifts, rendering current vaccines less effective over time. The development of a vaccine capable of providing broad and long-lasting protection against diverse influenza strains is critical for addressing both seasonal outbreaks and potential pandemics. This paper explores the strategies for designing antigens that could be utilized in the development of such a universal vaccine (Skarlupka et al., 2021). Influenza is a highly contagious respiratory illness caused by influenza viruses, primarily types A and B. The virus's ability to rapidly mutate leads to seasonal epidemics, which result in significant morbidity, mortality, and economic burden globally. According to the World Health Organization (WHO), annual influenza epidemics cause about 3 to 5 million cases of severe illness and approximately 290 000 to 650 000 deaths worldwide. Beyond these seasonal outbreaks, influenza poses a constant threat of pandemics, as seen with the H1N1 pandemic in 2009, which can have devastating consequences on public health systems and economies (Nguyen and Choi, 2021). Current influenza vaccines are primarily strain-specific, targeting surface proteins like hemagglutinin (HA) and neuraminidase (NA). Due to the frequent antigenic drift and shift of these viruses, annual reformulation of vaccines is required, which often leads to a mismatch between the vaccine strains and circulating viruses, thereby reducing vaccine efficacy. Additionally, the immune response generated by these vaccines is typically short-lived, necessitating yearly vaccination. Moreover, the current vaccines predominantly induce strain-specific antibodies that do not provide cross-protection against divergent influenza virus strains, highlighting the need for a more robust and universal vaccine approach (Nguyen and Choi, 2021). This study primarily discusses the current strategies for antigen design in the development of universal influenza vaccines and identifies key antigens and their roles in eliciting broad and cross-reactive immune responses. The research explores the potential of targeting the HA stem, NA, matrix proteins, and internal proteins as antigens to generate durable immunity against multiple influenza subtypes. It also evaluates the advantages and limitations of these antigens, providing a comprehensive overview of the challenges and opportunities in the development of a universal influenza vaccine.
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