Lipid matrix-based subunit vaccines: a structure-function approach to oral and parenteral immunization

Immunization is today the most effective defense mechanism against microbial infections. Although highly effective vaccines are currently available for a number of infectious diseases, vaccine formulations can still be improved in a number of important areas. The ability to induce antigen-specific humoral and cell-mediated immunity is crucial to the development of effective prophylactic and therapeutic vaccines for HIV and other pathogens. The approach of our laboratory has been to design and test simple, highly defined antigen-lipid complexes that would stimulate antibody and cell-mediated immune responses in the absence of any nonspecific immunological activators such as Freund's adjuvant, lipopolysaccharide (LPS), or alum. These studies have provided insight into the relationships between the properties of an immunogen and the induction of the desired immune responses. We have previously utilized this approach to define the minimal structures required for the induction of antibody responses. Our more recent studies have focused on defining the parameters involved in the induction of cell-mediated and mucosal immune responses. Toward this end we have developed a new type of subunit vaccine that is effective when given orally or intramuscularly, and elucidated structure-function relationships in peptide vaccines that affect induction of CD8+ cell responses.