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.