Journal of Vaccine Research 2024, Vol.14, No.4, 157-169 http://medscipublisher.com/index.php/jvr 165 7.2 Vaccine-Associated enhancement of infection Vaccine-associated enhancement of infection (VAEI) is a phenomenon where a vaccine inadvertently exacerbates the severity of the disease it is designed to prevent. This can occur through mechanisms such as antibody-dependent enhancement (ADE), where non-neutralizing antibodies facilitate viral entry into host cells, leading to increased viral replication and disease severity. While VAEI has been a concern in the development of vaccines for other viruses like dengue, it remains a potential risk in influenza vaccine development, especially for vaccines targeting conserved epitopes shared by multiple virus strains. Studies have shown that certain adjuvants, such as AS03, can mitigate this risk by promoting the production of broadly neutralizing antibodies and enhancing cellular immune responses (Goff et al., 2015). However, careful evaluation in preclinical and clinical studies is essential to ensure that new vaccine candidates do not inadvertently enhance infection or disease severity in vaccinated individuals. Future research should focus on understanding the immunological mechanisms underlying VAEI and developing vaccine formulations that minimize this risk while maximizing protective efficacy. 7.3 Long-Term efficacy and durability One of the key challenges in universal influenza vaccine development is ensuring long-term efficacy and durability of the immune response. Current seasonal vaccines typically require annual administration due to waning immunity and antigenic drift. In contrast, a universal vaccine would need to provide long-lasting protection against a broad range of influenza strains, including those that may emerge in the future. Recent advances have shown promise in this area; for example, a study demonstrated that a single dose of a recombinant adenovirus-based vaccine expressing conserved influenza antigens could induce immune responses that persisted for over a year without the need for boosting (Lo et al., 2021). Another approach involves the use of nanoparticle vaccines that enhance the longevity of the immune response by improving antigen presentation and retention in germinal centers, where long-term immune memory is generated (Gao et al., 2023). However, further research is needed to optimize these strategies and ensure that they provide robust, durable immunity across different populations and age groups. Addressing these challenges will be critical to realizing the goal of a universal influenza vaccine that can provide sustained protection over time. 8 Concluding Remarks The pursuit of a universal influenza vaccine has advanced considerably, driven by the need to overcome the limitations of current seasonal vaccines. The development of a universal influenza vaccine has focused on several innovative strategies, including targeting conserved regions of the virus, such as the hemagglutinin (HA) stalk, neuraminidase (NA), and matrix protein 2 (M2). Chimeric HA-based vaccines, virus-like particle (VLP)-based vaccines, and nanoparticle vaccines have shown promising results in both preclinical and early clinical studies. These approaches aim to elicit broadly neutralizing antibodies and robust T-cell responses that provide cross-protection against a wide range of influenza subtypes. However, challenges such as immunodominance, vaccine-associated enhancement of infection, and the durability of immune responses remain significant hurdles. Addressing these challenges will be crucial for the successful development and deployment of a universal influenza vaccine. The future of universal influenza vaccine development is promising, but it requires sustained efforts in both research and clinical evaluation. Advances in computational modeling, structural biology, and immunology are expected to play a pivotal role in designing vaccines that can overcome the issue of immunodominance and provide long-lasting protection. Additionally, the integration of novel adjuvants and delivery platforms, such as nanoparticle-based systems, will likely enhance the efficacy and durability of these vaccines. The success of these initiatives will depend on comprehensive preclinical studies and well-designed clinical trials that address safety, immunogenicity, and efficacy across diverse populations. Despite significant progress, the development of a universal influenza vaccine is far from complete. Continued research is essential to address the remaining challenges and to refine the strategies that have shown promise.
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