Liposomes as carriers of peptide antigens: induction of antibodies and cytotoxic T lymphocytes to conjugated and unconjugated peptides.
In the quest for effective immunization against complex diseases such as cancer, parasitic diseases, AIDS, and other viral infections, numerous peptides and recombinant proteins have been synthesized, examined for the ability to induce antibodies and CTLs, and tested for binding capability and therapeutic or prophylactic efficacy against the original target cell or organism. A liposome formulation, consisting of alum-adsorbed liposomes containing both a potent adjuvant, lipid A, and encapsulated or surface bound antigen, has had a record of safety and strong effectiveness for induction of antibodies in human vaccine trials. These same liposomes can also serve as effective vehicles for delivering conjugated or unconjugated peptides and proteins to antigen presenting cells for presentation via MHC class I and class II pathways for induction of CTLs and antibodies in experimental animal models. Liposomal lipid A appears to be extremely important, and is often a requirement, as an adjuvant for induction of CTLs against liposomal peptide antigens. Computer-generated molecular modelling analysis of small unconjugated or lipid-conjugated peptides strongly suggests that the expression of peptide antigen on the surface of the liposomes can be an important factor both in the induction of antibodies and in determining antibody specificities to small peptides. However, antigenic surface expression of liposomal peptide is not required for induction of CTLs. The data suggest that small synthetic peptides, synthesized with or without a lipid tail, or chemically conjugated to the surface of liposomes, might serve as effective antigenic epitopes, in combination with liposomal lipid A for induction of antibodies and CTLs.
Alving
C R
CR
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Koulchin
V
V
Glenn
G M
GM
Rao
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D010455:Peptides