title: Synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined HLA genotypes.
abstract: 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.
authors.affiliation: New York University School of Medicine, Dept. of Medical and Molecular Parasitology, New York, NY 10010, USA. Elizabeth.Nardin@med.nyu.edu
authors.forename: E H
authors.initials: EH
authors.lastname: Nardin
authors.forename: G A
authors.initials: GA
authors.lastname: Oliveira
authors.forename: J M
authors.initials: JM
authors.lastname: Calvo-Calle
authors.forename: Z R
authors.initials: ZR
authors.lastname: Castro
authors.forename: R S
authors.initials: RS
authors.lastname: Nussenzweig
authors.forename: B
authors.initials: B
authors.lastname: Schmeckpeper
authors.forename: B F
authors.initials: BF
authors.lastname: Hall
authors.forename: C
authors.initials: C
authors.lastname: Diggs
authors.forename: S
authors.initials: S
authors.lastname: Bodison
authors.forename: R
authors.initials: R
authors.lastname: Edelman
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D017780:Malaria Vaccines; D012503:Saponins; D014614:Vaccines, Synthetic; C078785:saponin QA-21V1