Journal of Vaccine Research 2024, Vol.14, No.4, 157-169 http://medscipublisher.com/index.php/jvr 160 immune response towards more conserved regions, such as the HA stalk and receptor-binding sites (RBS), which are less prone to antigenic drift and thus offer a more stable target for vaccine-induced immunity. The HA stalk, for instance, is a highly conserved structure across different influenza subtypes, making it an ideal target for broad-spectrum protection (Bajic et al., 2019). Recent advances in computational biology have greatly enhanced the ability to design immunogens that can precisely mimic these conserved epitopes, leading to the generation of broadly neutralizing antibodies (bnAbs). These bnAbs are capable of recognizing and neutralizing a wide range of influenza strains, offering a significant advantage over strain-specific antibodies typically induced by conventional vaccines. For example, computational tools have been used to design novel immunogens that stabilize these conserved epitopes, ensuring that they are presented to the immune system in their native conformation, which is crucial for eliciting an effective immune response (Sesterhenn et al., 2020). Additionally, multi-epitope vaccine constructs have been developed, combining several conserved regions into a single immunogen, thereby increasing the breadth and durability of the immune response. These constructs often include conserved regions from different viral proteins, such as HA, neuraminidase (NA), and matrix protein 2 (M2), to ensure comprehensive protection (Sharma et al., 2021). Despite the promise of epitope-focused design, challenges remain, including the need to overcome the immune system's preference for immunodominant but variable regions, such as the HA head. Efforts are ongoing to fine-tune the presentation of these conserved epitopes to ensure that they elicit a strong and focused immune response. Overall, epitope-focused design represents a promising avenue for the development of a truly universal influenza vaccine, with the potential to provide long-lasting protection against both seasonal and pandemic influenza strains. 4.2 Prime-Boost strategies Prime-boost strategies have emerged as a potent approach in enhancing the efficacy of vaccines, particularly in the context of universal influenza vaccine development. This strategy involves administering a "prime" dose of one type of vaccine, followed by one or more "boost" doses of either the same or a different type of vaccine. The goal is to strengthen and sustain the immune response, particularly against conserved viral antigens that are crucial for broad protection. Prime-boost strategies are especially effective in focusing the immune response on less immunogenic but conserved regions of the virus, such as the HA stalk, which is essential for developing broad-spectrum immunity. A typical prime-boost regimen might involve a DNA vaccine as the prime, which introduces the antigen and initiates the immune response, followed by a viral vector or protein-based boost that amplifies this response. This approach has been shown to significantly enhance both humoral and cellular immunity, resulting in higher titers of neutralizing antibodies and stronger T-cell responses. For instance, studies using a DNA prime followed by a recombinant viral vector boost have demonstrated robust production of stalk-specific antibodies, which are critical for cross-protection against various influenza strains (Goodman et al., 2011). The effectiveness of prime-boost strategies is further supported by clinical trials and preclinical studies that show improved protection against heterologous influenza strains. For example, a study involving a prime-boost regimen using H5N1 DNA and a protein-based boost elicited antibodies capable of neutralizing multiple subtypes of influenza A viruses, highlighting the potential of this approach in achieving cross-protection (Joyce et al., 2016). However, challenges remain, such as the potential for vaccine-associated enhancement of infection and the need to optimize the timing and composition of the prime and boost doses to maximize efficacy while minimizing adverse effects (Jang and Seong, 2014). Moreover, the practicality of implementing prime-boost strategies in large populations, particularly in terms of cost and logistics, is a significant consideration. Despite these challenges, prime-boost strategies hold great promise for the development of universal influenza vaccines, as they offer a means to direct the immune response toward conserved viral components, thereby providing broader and more durable protection.
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==