Journal of Vaccine Research 2024, Vol.14, No.4, 157-169 http://medscipublisher.com/index.php/jvr 163 as enhancing antigen presentation, promoting the recruitment of immune cells to the site of vaccination, and inducing broader immune responses against heterologous viral strains (Ng et al., 2016; Tregoning et al., 2018). 6 Case Study: Preclinical and Clinical Development The development of universal influenza vaccines has advanced significantly through various preclinical and clinical studies. These studies have focused on novel antigen designs that target conserved regions of the influenza virus, aiming to provide broad and long-lasting protection. 6.1 Chimeric HA-Based vaccines Chimeric hemagglutinin (HA)-based vaccines are designed to elicit immune responses against the conserved stalk domain of the HA protein, rather than the highly variable head domain. This approach aims to generate broadly neutralizing antibodies that can provide cross-protection against multiple influenza subtypes. Preclinical studies have shown that chimeric HA constructs, which combine the stalk domain of one influenza strain with the head domain of another, can effectively focus the immune response on the stalk region. For instance, a study demonstrated that a chimeric HA vaccine with a conserved HA stalk from H1N1 combined with an exotic head domain from H5N1 elicited strong CD4+ and CD8+ T cell responses, providing broad protection against various influenza strains (Figure 2) (Liao et al., 2020). Figure 2 depicts the neutralizing activity of different constructs of chimeric hemagglutinin (cHA) vaccines and their induced CD8+ T cell responses (Adapted from Liao et al., 2020) Note: The experiments demonstrated that the cHA vaccine using the H5 head and H1 stalk structure effectively induced cross-neutralizing activity against both H1N1 and H5N1 viruses. Additionally, the cHA vaccine also induced a strong CD8+ T cell
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