Mucosal and Systemic Immunization using Cochleate and Liposome Vaccines

For more than a decade our laboratories have been combining concepts in biochemistry, virology and immunology, in order to develop a conceptual basis for vaccine design. Our long term goals have been to construct simple and well defined immunogens which would stimulate specific immune responses in vivo. Using this approach, we hypothesized that it should be possible to define the structural and biochemical parameters of an immunogen that are necessary and sufficient to stimulate designated effector arms of the immune system. Through the use of covalently coupled peptide complexes, we have been able to define minimal requirements for the induction of humoral immune responses. Minimal requirements for the induction of CD 8 +, MHC Class I restricted Cytotoxic T Lymphocytes have been defined through the use of fusogenic proteoliposomes and simple peptide-lipid complexes (1,2). Finally, we have described a unique, highly stable, lyophilizable, lipid-based vaccine carrier and delivery formulation called protein cochleates. Protein cochleates are highly effective vaccines when given orally or parenterally, generating strong, long term circulating and mucosal, antibody and cell mediated responses, and protection from mucosal challenge with live virus. Our current focus is to combine these concepts and structures to the preparation of subunit vaccines for humans.