Journal of Vaccine Research 2024, Vol.14, No.4, 157-169 http://medscipublisher.com/index.php/jvr 158 2 Rationale for Universal Influenza Vaccine Development The development of a universal influenza vaccine (UIV) is a critical objective in public health due to the significant limitations of current seasonal vaccines and the continuous threat posed by influenza viruses (Xu et al., 2024). 2.1 Antigenic drift and shift Influenza viruses are notorious for their ability to undergo frequent genetic changes, which can manifest as either antigenic drift or antigenic shift. Antigenic drift refers to the gradual accumulation of mutations in the virus's surface proteins, particularly hemagglutinin (HA) and neuraminidase (NA), which leads to the emergence of new strains that can evade the immune system. This process is responsible for the need to update seasonal influenza vaccines annually. On the other hand, antigenic shift is a more abrupt and significant genetic change that occurs when two different strains of influenza viruses infect the same cell and exchange genetic material. This can result in a new subtype that is substantially different from previous strains, often leading to pandemics due to the lack of pre-existing immunity in the population (Pica and Palese, 2013; Nguyen and Choi, 2021; Wang et al., 2022). The ability of the influenza virus to undergo these genetic changes poses significant challenges for vaccine development, as current vaccines are designed to target specific strains. As a result, the continuous evolution of the virus necessitates the frequent reformulation of vaccines, often leading to mismatches between the vaccine and circulating strains, which reduces vaccine efficacy (Madsen and Cox, 2020). This highlights the urgent need for a universal influenza vaccine that can provide broad and long-lasting protection against a wide range of influenza strains. 2.2 Limitations of current seasonal vaccines Current seasonal influenza vaccines have several limitations that undermine their effectiveness. These vaccines are primarily designed to target specific strains predicted to circulate in the upcoming flu season. However, the unpredictability of antigenic drift and shift often results in a mismatch between the vaccine strains and the actual circulating viruses, leading to reduced vaccine efficacy. For instance, during the 2017-2018 flu season, the vaccine was only about 40% effective due to such a mismatch (Jang and Seong, 2019). Additionally, the immunity conferred by these vaccines is short-lived, necessitating annual vaccination. This is particularly problematic for at-risk populations, such as the elderly, who may not respond as robustly to vaccination (Paules et al., 2017). Moreover, current vaccines do not provide cross-protection against diverse influenza subtypes, leaving individuals vulnerable to novel strains that may cause pandemics (Petrie and Gordon, 2018). The limitations of these vaccines underscore the need for a universal influenza vaccine that can provide broad and durable protection against multiple strains, reducing the need for annual vaccinations and offering better protection against emerging pandemic strains (Nguyen and Choi, 2021). 2.3 The case for a universal vaccine The development of a universal influenza vaccine (UIV) is essential to overcome the limitations of current seasonal vaccines and to provide long-lasting protection against a wide range of influenza strains. A UIV would target conserved regions of the influenza virus, such as the HA stalk and NA, which are less prone to antigenic drift and shift, thus offering broad-spectrum immunity (Skarlupka et al., 2021). Recent advances in vaccine technology, such as the use of novel adjuvants and delivery platforms, have shown promise in enhancing the immunogenicity of these conserved epitopes, potentially leading to the development of a UIV (Viboud et al., 2020). Furthermore, the integration of computational tools and structural biology has facilitated the rational design of vaccine candidates that can elicit broadly neutralizing antibodies and cross-reactive T cell responses (Sangesland and Lingwood, 2021). The potential of a UIV to provide comprehensive protection against both seasonal and pandemic influenza viruses would be a significant public health achievement, reducing the global burden of influenza and improving pandemic preparedness (Jang and Seong, 2019; Wang et al., 2022).
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