More effective vaccines are nowadays becoming a reality as we learn more about inducing appropriate immune responses particularly through the use of immune modulating molecules including ligands for Toll-like receptors (TLRs). The use of such ligands, such as Pam2Cys (S-[2,3-bis(palmitoyloxy)propyl]cysteine) which targets TLR2, provides a rational approach to improving the immunogenicity of soluble protein antigens which are otherwise weakly immunogenic. Using branched and charged lipopeptides this study describes experiments designed with a view to improve the efficacy of protein-based vaccines.
Cationic (R4Pam2Cys) and anionic (E8Pam2Cys) Pam2Cys-based lipopeptides were used to enhance the immunogenicity of protein antigens through electrostatic association. The influence of these lipopeptides on antibody and cellular responses induced by vaccination were examined in wild type mice and transgenic mice deficient in TLR2 or CD4+ T cells. We also investigated the quality of these responses in reducing disease severity associated with lethal and non-lethal influenza virus infection.
Our results demonstrate that formulation of these lipopeptides with soluble protein antigens can elicit robust cell-mediated and humoral immune responses which are dependent on TLR2 signaling and CD4+ T cell help. These immune responses played a critical role in protecting animals from challenge with influenza virus.
The potential of this vaccine to enhance both antibody and cytotoxic T cell responses provides a strategy for the development of vaccines against pathogens including influenza virus and tuberculosis.