LIPID MATRIX-BASED SUBUNIT VACCINES - A STRUCTURE-FUNCTION APPROACH TO ORAL AND PARENTERAL IMMUNIZATION

Immunization is today the most effective defense mechanism against mic robial infections. Although highly effective vaccines are currently av ailable for a number of infectious diseases, vaccine formulations can still be improved in a number of important areas. The ability to induc e antigen-specific humoral and cell-mediated immunity is crucial to th e development of effective prophylactic and therapeutic vaccines for H IV and other pathogens. The approach of our laboratory has been to des ign 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 insigh t into the relationships between the properties of an immunogen and th e induction of the desired immune responses. We have previously utiliz ed this approach to define the minimal structures required for the ind uction of antibody responses.(1,2) Our more recent studies have focuse d on defining the parameters involved in the induction of cell-mediate d and mucosal immune responses. Toward this end we have developed a ne w type of subunit vaccine that is effective when given orally or intra muscularly, and elucidated structure-function relationships in peptide vaccines that affect induction of CD8(+) cell responses.