title: Human leukocyte antigen class II alleles influence levels of antibodies to the Plasmodium falciparum asexual-stage apical membrane antigen 1 but not to merozoite surface antigen 2 and merozoite surface protein 1.
abstract: The apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine for Plasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP1(19)) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP1(19) variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP1(19) but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP1(19) variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated.
authors.affiliation: Departments of Pediatrics, Georgetown University, Washington, DC 20057, USA. johnsoa2@georgetown.edu
authors.forename: Armead H
authors.initials: AH
authors.lastname: Johnson
authors.forename: Rose G F
authors.initials: RG
authors.lastname: Leke
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Mendell
authors.forename: Dewon
authors.initials: D
authors.lastname: Shon
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Suh
authors.forename: Dennis
authors.initials: D
authors.lastname: Bomba-Nkolo
authors.forename: Viviane
authors.initials: V
authors.lastname: Tchinda
authors.forename: Samuel
authors.initials: S
authors.lastname: Kouontchou
authors.forename: Lucy W
authors.initials: LW
authors.lastname: Thuita
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: van der Wel
authors.forename: Alan
authors.initials: A
authors.lastname: Thomas
authors.forename: Anthony
authors.initials: A
authors.lastname: Stowers
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Ainong
authors.initials: A
authors.lastname: Zhou
authors.forename: Diane W
authors.initials: DW
authors.lastname: Taylor
authors.forename: Isabella A
authors.initials: IA
authors.lastname: Quakyi
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005787:Gene Frequency; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006451:Hemoglobin, Sickle; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C065974:merozoite surface protein 2, Plasmodium