Synthetic Malaria Peptide Vaccine Elicits High Levels of Antibodies in Vaccinees of Defined HLA Genotypes

• Published in: The Journal of infectious diseases Vol. 182; no. 5; pp. 1486 - 1496
• Main Authors: Nardin, Elizabeth H., Oliveira, Giane A., Calvo-Calle, J. Mauricio, Castro, Z. Rosa, Nussenzweig, Ruth S., Schmeckpeper, Barbara, Hall, B. Fenton, Diggs, Carter, Bodison, Sacared, Edelman, Robert
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-11-2000; University of Chicago Press; Oxford University Press
• Subjects: Adult; Animals; Antibodies; Antibodies, Protozoan - biosynthesis; Biological and medical sciences; circumsporozoite protein; Cohort Studies; Epitopes; Female; Fundamental and applied biological sciences. Psychology; Genotype; Genotypes; histocompatibility antigen HLA; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Immunization; Major Articles; Malaria; Malaria Vaccines - immunology; Male; Plasmodium falciparum; Plasmodium falciparum - immunology; Protozoa; Saponins - pharmacology; Sporozoites; T lymphocytes; Transponders; Tropical medicine; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Volunteerism; Human; Protozoa; HLA-System; Apicomplexa; Protozoal disease; Immune response; Malaria; Peptides; Antibody; Class II histocompatibility antigen; Genotype; Vaccine; Parasitosis; HLA-DR-Locus; Infection; HLA-DQ-Locus; Plasmodium falciparum; Immunogenicity; Humoral immunity
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315871

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum—infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.