Journal of Vaccine Research 2024, Vol.14, No.2, 40-53 http://medscipublisher.com/index.php/jvr 41 this study offers a comprehensive overview of the current state of UIV development. It also discusses the challenges and prospects of achieving a truly universal influenza vaccine, focusing on the potential for broad and long-lasting immunity. Understanding and applying mechanisms of broad protection is crucial for developing vaccines with durability and wide-ranging protective capabilities. The development of such vaccines could not only reduce the need for annual vaccine updates but also enhance preparedness for unexpected influenza outbreaks. 2 Need for Universal Influenza Vaccines Influenza viruses pose a significant public health challenge due to their high mutation rates and the resulting antigenic drift and shift, which necessitate frequent updates to seasonal vaccines. Current influenza vaccines primarily target the hemagglutinin (HA) and neuraminidase (NA) proteins, which are prone to rapid evolution. This leads to a mismatch between the vaccine strains and circulating viruses, reducing vaccine efficacy and leaving populations vulnerable to outbreaks (Jang and Seong, 2019; Nachbagauer et al., 2021; Lo et al., 2021). The unpredictability of influenza virus strains and the lengthy process of vaccine production further complicate timely and effective immunization efforts (Freyn et al., 2020; Vogel and Manicassamy, 2020). The development of a universal influenza vaccine (UIV) aims to address these challenges by providing broad and long-lasting protection against diverse influenza strains. Such a vaccine would target conserved viral antigens, reducing the need for annual reformulation and offering a more robust defense against both seasonal and pandemic influenza viruses. The National Institute of Allergy and Infectious Diseases (NIAID) has prioritized the development of UIVs to mitigate the substantial public health burden associated with influenza (Scorza et al., 2016; Vogel and Manicassamy, 2020). 2.1 Limitations of existing vaccines Current influenza vaccines have several limitations that hinder their effectiveness. One major issue is the reliance on strain-specific neutralizing antibodies against the variable globular head domain of the HA protein. This specificity necessitates frequent updates to the vaccine composition to match the circulating strains, which is a time-consuming and often imprecise process (Jazayeri and Poh, 2019; Nachbagauer et al., 2021). Additionally, the efficacy of these vaccines can vary widely from year to year, depending on the accuracy of strain predictions and the degree of antigenic match (Bernstein et al., 2019; Vogel and Manicassamy, 2020). Moreover, existing vaccines primarily induce humoral immune responses, with limited activation of cell-mediated immunity against conserved internal viral proteins. This narrow focus on surface antigens leaves gaps in protection, particularly against drift and shift variants. The need for annual vaccination and the potential for significant mismatches between vaccine and circulating strains underscore the urgent need for more broadly protective vaccine strategies (Vemula et al., 2017; Jazayeri and Poh, 2019). 2.2 Benefits of a universal vaccine A universal influenza vaccine would offer several significant benefits over current seasonal vaccines. By targeting conserved viral antigens, such as the HA stalk, neuraminidase, and internal proteins like nucleoprotein (NP) and matrix 2 (M2), a UIV could provide broad and durable protection against a wide range of influenza strains, including those that have undergone antigenic drift or shift (Freyn et al., 2020; Nachbagauer et al., 2021; Lo et al., 2021). This broad-spectrum protection would reduce the need for annual vaccine updates and improve overall vaccine efficacy (Jang and Seong, 2019; Vogel and Manicassamy, 2020). Furthermore, a UIV could enhance pandemic preparedness by providing a baseline level of immunity against emerging influenza strains, potentially mitigating the impact of future pandemics. The development of novel vaccine platforms, such as nucleoside-modified mRNA and chimeric HA-based vaccines, has shown promise in eliciting strong and long-lasting immune responses in preclinical and clinical studies (Figure 1) (Bernstein et al., 2019; Freyn et al., 2020; Nachbagauer et al., 2021). These advancements highlight the potential of UIVs to revolutionize influenza prevention and control, offering a more reliable and comprehensive approach to combating this persistent public health threat (Jazayeri and Poh, 2019).
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