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High levels of antibodies to multiple antigens may be more strongly associated with protection from infection than antibodies to a single antigen. Antibody-associated protection against Plasmodium falciparum infection was assessed in a cohort of 68 adults living in an area of holoendemic malaria in Kenya. Antibodies to the pre-erythrocytic antigens circumsporozoite protein (CSP), liver-stage antigen-1 (LSA-1), thrombospondin-related adhesive protein (TRAP), and blood-stage antigens apical membrane antigen-1 (AMA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein 1 (MSP-1) were tested. Peptides were used for CSP (NANP repeat) and LSA-1 (central repeat), and recombinant antigens were used for TRAP (aa D48–K394), AMA-1 (ectodomain, non-glycosylated), EBA-175 (non-glycosylated), and MSP-1 (MSP-119). Weekly microscopy testing for P. falciparum infection was performed over a 12-week period after drug-mediated clearance of P. falciparum parasitemia. Individuals with high levels of IgG antibodies (> 2 arbitrary units) to CSP, LSA-1, and TRAP had a 57% decrease in the risk of infection (95% confidence interval = 20–77%, P = 0.016). This decreased risk remained significant after adjustment for age, prior parasitemia, bed net use, sickle cell trait, and village of residence. In contrast, protection against infection did not correlate with high levels of IgG antibodies to blood-stage antigens or IgM antibodies to pre-erythrocytic or blood-stage antigens. High levels of IgG antibodies to CSP, LSA-1, and TRAP may be useful immune correlates of protection against P. falciparum infection in malaria-endemic populations.
Received November 4, 2004. Accepted for publication December 30, 2004.
Acknowledgments: We thank the Kanyawegi site field assistants for their daily follow-up of study participants and Jackson Abuya and Livingstone Wanyama for microscopy evaluation. We also thank the Office of the Director of the Kenya Medical Research Institute for permission to publish this study.
Financial support: This work was supported by grant AI43906 form the U.S. Public Health Service.
* Address correspondence to Chandy C. John, Rainbow Center for International Child Health, Rainbow Babies and Children’s Hospital, RBC 487, Case Western Reserve University, 11100 Euclid Avenue, MS6008, Cleveland, OH 44106. E-mail: chandy.john{at}case.edu
Author’ addresses: Chandy C. John, Rainbow Center for International Child Health, Rainbow Babies and Children’s Hospital, RBC 487, Case Western Reserve University, 11100 Euclid Avenue, MS6008, Cleveland, OH 44106, Telephone: 216-844-3645, Fax: 216-844-8362, E-mail: chandy.john{at}case.edu. Ann M. Moormann, Daniel C. Pregibon, Marilyn M. McHugh, and James W. Kazura, Center for Global Health and Diseases, Case Western Reserve University School of Medicine, 2103 Cornell Road, Room 4128, Wolstein Research Building, Fourth Floor, Cleveland, OH 44106-7286. Telephone: 216-368-4822, Fax: 216-368-4825, E-mails: ann.moormann{at}case.edu, pregibon{at}mit.edu, marilyn.mchugh{at}case.edu, and james.kazura{at}case.edu. Peter Odada Sumba, Kenya Medical Research Institute, Box 1576, Kisumu, Kenya, Telephone: 254-057-22989, E-mail: pos{at}case.edu. David L. Narum, Malaria Vaccine Development Branch, National Institutes of Health, Twinbrook I Facility, 5640 Fishers Lane, Rockville, MD 20852, Telephone: 301-435-2185, Fax: 301-480-1962, E-mail: dnarum{at}niaid.nih.gov. David E. Lanar, Department of Immunology, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, Telephone: 301-319-9003, Fax: 202-318-7594, E-mail: david. lanar{at}na.amedd.army.mil. Mark D. Schluchter, Division of Clinical Epidemiology, Department of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-6003, Telephone: 216-844-2391, Fax: 216-844-6265, E-mail: mark.schluchter{at}case.edu.
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