HLA-DR: molecular insights and vaccine design

Vaccines are one of the most cost effective methods to control infectious diseases and at the same time one of the most complex products of the pharmaceutical industry. In contrast to other drugs, vaccines are used mainly in healthy individuals, often in children. For this reason, very high standards are set for their production. Subunit vaccines, especially peptide vaccines, can provide a safe and cost-effective alternative to vaccines produced from attenuated or inactivated pathogen preparations. Biochemical and structural studies of class II MHC-peptide complexes are beginning to provide a conceptual foundation for the rational design of subunit and peptide vaccines. In this review, we show how analysis of peptide-class II MHC complexes together with developing understanding of antigen processing pathways has opened the door to understanding the major rules that govern selection of T cell epitopes. We review progress towards computational prediction of such epitopes, and efforts to evaluate algorithms that incorporate various structural and/or biochemical aspects of the MHC-peptide interaction. Finally, using malaria as a model, we describe the development of a minimal subunit vaccine for the human malaria parasite Plasmodium falciparum.