Journal of Vaccine Research 2024, Vol.14, No.2, 40-53 http://medscipublisher.com/index.php/jvr 46 T-cell responses. Combining these vectors with chimeric hemagglutinin constructs has shown promising results in providing broad protection against influenza virus challenges in mice (Arunkumar et al., 2019). This strategy highlights the potential of viral vector-based vaccines to induce durable and broad immune responses, making them a viable candidate for universal influenza vaccines. 4.2 Recombinant protein vaccines Recombinant protein vaccines focus on using conserved influenza antigens to elicit immune responses. One approach involves the use of fusion proteins containing multiple copies of the ectodomain of matrix protein 2 (M2e), a highly conserved antigen. Incorporating these fusion proteins into nanoparticle-based delivery systems has shown enhanced immune protection against live influenza virus challenges. For instance, a study demonstrated that a fusion protein with three copies of M2e, when incorporated into porous maltodextrin nanoparticles, provided strong and broadly protective immunity against heterosubtypic influenza virus infections (Bernasconi et al., 2018). Another promising strategy involves the use of recombinant outer membrane vesicles (OMVs) engineered to display M2e antigens. These OMVs have been shown to elicit strong IgG titers and provide 100% survival against lethal influenza challenges in mice. The protection was largely driven by antibody-mediated immunity, indicating the potential of OMVs as a platform for universal influenza vaccine development (Rappazzo et al., 2016). Additionally, recombinant baculovirus vaccines expressing multiple M2e copies and adjuvants have demonstrated cross-clade protection against H5N1 influenza viruses, further supporting the efficacy of recombinant protein vaccines in providing broad protection (Zhang et al., 2016). 4.3 mRNA vaccines mRNA vaccines represent a novel approach to universal influenza vaccine development. These vaccines utilize lipid nanoparticle-encapsulated, nucleoside-modified mRNA to deliver genetic instructions for the production of conserved influenza antigens within host cells. A study demonstrated that mRNA vaccines encoding a combination of conserved influenza antigens, such as hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein, induced strong and broad immune responses in mice. The immunity conferred by these vaccines provided protection from pandemic H1N1 virus challenges at high doses, highlighting their potential for broad protection (Freyn et al., 2018). The use of mRNA vaccines offers several advantages, including rapid development and production, as well as the ability to induce both humoral and cellular immune responses. The broad protective potential of mRNA vaccines has been confirmed by challenges with a panel of group 1 influenza A viruses, supporting their advancement as universal influenza vaccine candidates (Freyn et al., 2018). This innovative approach leverages the flexibility and efficacy of mRNA technology to address the challenges posed by rapidly evolving influenza viruses. 4.4 Adjuvants and delivery systems Adjuvants and delivery systems play a crucial role in enhancing the efficacy of universal influenza vaccines. One example is the use of Advax-SM adjuvant in combination with an M2-based influenza vaccine. This formulation has shown protective efficacy in both maternal and neonatal immunization models, providing protection against diverse influenza A strains. The adjuvant enhanced the immune response, leading to high antibody levels and significant reduction in lung virus load in immunized pups (Sakala et al., 2021). Another innovative approach involves the use of recombinant fusion proteins linking influenza M2e to adjuvants such as Onchocerca volvulus activation associated protein-1 (ASP-1). These fusion proteins have demonstrated strong humoral and cellular immune responses, providing significant cross-clade protection against divergent H5N1 viruses. The use of adjuvants like ASP-1 enhances the immunogenicity of the vaccine, making it a promising candidate for universal influenza vaccine development. Additionally, the incorporation of adjuvants such as LTB in recombinant baculovirus vaccines has shown improved survival and decreased lung virus shedding in mice, further supporting the role of adjuvants in enhancing vaccine efficacy (Zhang et al., 2016).
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