Immunization has proven to be one of the most effective means to prevent disease. Despite this success, effective vaccines are lacking for many important diseases (e.g. HIV & malaria), and the use of vaccines to treat disease (e.g. cancers & autoimmune disease) remains an exciting prospect that awaits its full exploitation. Developing new vaccines in many cases will require a movement from traditional whole organism approaches, towards chemically defined systems (e.g. subunit and DNA vaccines), and their administration with powerful immunostimulatory compounds (adjuvants). With relatively few safe adjuvants for human use, novel adjuvant systems are essential for producing new vaccines.
We have developed subunit vaccines incorporating defined peptide antigens attached to lipid-based adjuvants. The immune response against these vaccines was significantly enhanced compared to the administration of peptide antigens with the commercial adjuvant alum, and allows for stimulation of both antibody and cellular immunity, as well as mucosal “needle free” vaccine administration. The use of peptide antigens however imposes limits on the amount of antigenic information that can be incorporated into a vaccine. We have therefore developed methods that enable the site-specific conjugation of lipid adjuvants onto expressed denatured or folded protein antigens. With recent advances in antigen identification providing numerous protective antigens suitable for subunit vaccine development, such an approach provides a more efficient means to develop lipid adjuvanted vaccines. These techniques have facilitated the simple and efficient production of homogeneous, chemically defined lipoprotein vaccines targeting group A streptococcus, incorporating combinations of conserved and protective peptide and protein antigens. These vaccines formed particles in the low nanometer size range (~ 40 nm), ideal for eliciting humoral immune responses. Following administration to mice, antigen-specific IgG antibodies were elicited against each incorporated antigen, without need for added adjuvant, or signs of toxicity.