Influenza disease is a global health issue. It causes significant morbidity and mortality through seasonal epidemics. Through rapid antigenic variation, influenza causes seasonal epidemics and potentially more serious pandemics. They are largely controlled through yearly vaccinations that reduce morbidity and mortality. In addition, the vast majority of influenza vaccines are based on trivalent inactivated vaccines (TIV). These detergent-split vaccines against three viral strains: influenza A (H1N1), influenza A (H3N2), and influenza B strain thereby promoting a humoral immune response towards glycoproteins hemagglutinin (HA) and neuraminidase (NA). Monophosphoryl lipid A (MPL) is an acylated diglucosamine derivative of lipid A. It is a toll-like receptor 4 (TLR4) adjuvant, and it has an acceptable safety and efficacy profile. In this study, GSK1795091 can be an adjuvant for enhancing vaccine-induced protection against influenza infection.
GSK1795091 (CRX-601) is an immunologic stimulator and synthetic TLR4 agonist. In addition, GSK1795091 also has antitumor activity. Furthermore, Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generates strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Moreover, intranasal vaccination with CRX-601 adjuvanted vaccines promotes antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells. GSK1795091 also is an immunologic stimulator. It enhances the antitumor immune response in combination with other immunomodulatory agents. They include agonists of OX40 and inducible costimulator or antagonists of programmed cell death protein 1, through induction of inflammatory cytokines (such as TNF-α and IL-6), enhancing antigen presentation. It also stimulates leukocyte activation and tumor infiltration.
In summary, GSK1795091 is a TLR4 agonist. It also is a vaccine adjuvant to enhance both mucosal and systemic immunity to influenza virus vaccines.