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Infection and Immunity, May 2004, p. 2762-2771, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2762-2771.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Armead H. Johnson,1* Rose G. F. Leke,2,3 Nancy R. Mendell,4 Dewon Shon,4 Young Ju Suh,5,6 Dennis Bomba-Nkolo,2 Viviane Tchinda,3 Samuel Kouontchou,3 Lucy W. Thuita,7 Anne Marie van der Wel,8 Alan Thomas,8 Anthony Stowers,9 Allan Saul,9,10 Ainong Zhou,7 Diane W. Taylor,7 and Isabella A. Quakyi7

Departments of Pediatrics,1 Biology, Georgetown University, Washington, D.C.,7 Faculty of Medicine and Biomedical Sciences,2 The Biotechnology Center, University of Yaounde I, Yaounde, Cameroon,3 Department of Applied Mathematics, State University of New York, Stony Brook, New York,4 Department of Statistics, Seoul National University,5 Clinical Research Institute, Seoul National University Hospital, Seoul, Korea,6 Biomedical Primate Research Centre, Rijswijk, The Netherlands,8 Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,9 The Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia,10

Received 6 January 2003/ Returned for modification 6 March 2003/ Accepted 1 February 2004

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 (MSP119) 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 MSP119 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 MSP119 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 MSP119 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.

* Corresponding author. Mailing address: Georgetown University Medical School, PCS Bldg.-LD8D, 3800 Reservoir Rd., N.W., Washington, DC 20057. Phone: (202) 687-1529. Fax: (202) 687-7161. E-mail: johnsoa2{at}georgetown.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2004, p. 2762-2771, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2762-2771.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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