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* Department of Biology, Georgetown University, Washington D. C. 20057;
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; and
Faculty of Medicine and Biomedical Sciences, Biotechnology Center, University of Yaoundé I, Yaoundé, Cameroon
Plasmodium falciparum infection during pregnancy can lead to the transplacental passage of malarial Ags that are capable of inducing acquired immune responses in the fetus. Studies have identified cytokines produced by malaria-specific cord blood (CB) T cells, but information on fetal B cells is limited. Thus, CB mononuclear cells from 120 Cameroonian newborns were cultured for 7 days in vitro and supernatants were assessed by ELISA for Abs to an extract of malarial schizonts (MA), recombinant apical merozoite Ag 1 (AMA-1), the 42-kDa C-terminal region of merozoite surface protein 1 (MSP-142), a B epitope of ring-infected erythrocyte surface Ag (RESA), and the dominant B epitope of the circumsporozoite protein (CSP). Only 12% of supernatants contained IgM to MA but 78% had IgG to one or more malarial Ags, with 53% having IgG to AMA-1, 38% to MSP-142, 3% to RESA, and 0% to CSP. The Abs to AMA-1 and MSP-142 were predominantly IgG1 and IgG3. CB mononuclear cells were also tested for the ability to secrete cytokines in response to MA and a pool of conserved MSP-1 T cell epitopes. Among the Ag-reactive samples, 39.3% produced only Th2-type cytokines, whereas 60.6% produced a combination of Th1- and Th2-type cytokines. Although a Th2 bias was observed, the in utero cytokine environment was adequate to support isotype switching to cytophilic IgGs, the isotypes that are protective in adults. Because many infants living in a low transmission area are born with malaria-specific B and T cells, the influence of in utero priming on neonatal immunity merits further investigation.
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1 This work was supported by National Institutes of Health Grant UO1 AI43888. S.M. was supported by a training grant from the Fogarty International Center (5 D43 TWO1264).
2 Address correspondence and reprint requests to Dr. Diane Wallace Taylor, Department of Tropical Medicine, Asia-Pacific Institute of Tropical Medicine and Infectious Diseases, John A. Burns School of Medicine, 651 Ilalo Street, Honolulu, HI, 96813. E-mail address: taylordw{at}georgetown.edu
3 Abbreviations used in this paper: CB, cord blood; AMA-1, apical merozoite Ag 1; CSP, circumsporozoite protein; IFA, indirect fluorescent antibody assay; IRBC, infected red blood cells; MA, extract enriched for schizont-stage malarial parasites; MC, mononuclear cell; MSP-1, merozoite surface protein-1; MSP-119, 19-kDa fragment of MSP-1; MSP-142, 42-kDa fragment of MSP-1; NRBC, noninfected RBC; RESA, ring-infected erythrocyte surface antigen; SI, stimulation index.
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