Virus-like Particles As Vaccine Adjuvants

Adjuvants are available to promote the generation of antibodies to an antigen following immunization. However, many of these adjuvants do not enhance priming of cytotoxic T lymphocytes (CTL). The reason for this lies in the existence of two alternative antigen processing pathways, leading to stimulation of CD4⁺ T cells, and, in turn, to the generation of antibodies, or stimulation of CD8⁺ CTL. In general, exogenous proteins enter the antigen presenting cell (APC) by endocytosis. Peptides produced by proteolytic degradation of these proteins bind to major histocompatibility complex (MHC) Class II molecules that travel to the surface of the cell before stimulating CD4⁺ T cells. Peptides derived from cytoplasmic proteins are translocated into the endoplasmic reticulum and bind to MHC Class I molecules. When these reach the surface of the APC, they prime CD8⁺ CTL. Thus to generate a CTL response following immunization, it is necessary to feed peptides into the correct processing pathway. This can be done by expressing the antigen inside the APC, using a DNA vaccine or recombinant virus. DNA vaccines can be produced easily, but there are still concerns over the long-term safety of this new type of vaccine, and the CD8⁺ T-cell response may only be moderate (1 ). Recombinant viruses are more difficult to prepare, and there are safety concerns over the use of some viruses as vaccines. However, recombinant virus-like particles (VLPs) are a safe and highly immunogenic alternative. These small particles consisting of one or more viral coat proteins can act as an adjuvant by carrying peptide sequences inside the APC and feeding into the “endogenous” processing pathway (2 ,3 ), a phenomemon known as “cross-priming.” No additional adjuvant is needed. If VLPs are administered with alum, CTL priming does not take place, although the antibody response to the VLPs is enhanced (4 ,5 ).