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* Malaria Vaccine Development Branch and
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and
Malaria Research and Training Center, Department of Hematology and Parasitology, University of Bamako, Bamako, Mali
Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the United States with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active Abs judged by an in vitro parasite growth inhibition assay (GIA). However, the same vaccine in Malian adults did not increase biological activity, although it elevated ELISA titers. Because GIA has been used to evaluate the biological activity of Abs induced by blood stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific Abs from both U.S. vaccinees and nonvaccinated individuals living in a malaria-endemic area of Mali and performed ELISA and GIA. Both AMA1-specifc Abs induced by vaccination (U.S.) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians’ IgG that did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 Abs from U.S. vaccinees; in contrast, U.S.-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specific IgGs in the Mali-non-AMA1 IgGs. The fact that both U.S.- and Mali-AMA1-specific Abs showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific Ab by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of Abs induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood stage malaria vaccine.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was funded in part by the PATH/Malaria Vaccine Initiative and the Intramural Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Kazutoyo Miura, 12441 Parklawn Drive, Twinbrook 2, Room 107, Rockville, MD 20852. E-mail address: kmiura{at}niaid.nih.gov, or Dr. Carole A. Long, 12735 Twinbrook Parkway, Twinbrook 3, Room 3W-13, Rockville, MD 20852. E-mail address: clong{at}niaid.nih.gov
3 Current address: PATH Malaria Vaccine Initiative, Bethesda, MD.
4 Current address: Albert B. Sabin Vaccine Institute, Washington, DC.
5 Current address: Division of Imaging Sciences, King’s College London, The Rayne Institute, Thomas’ Hospital, London, United Kingdom.
6 Abbreviations used in this paper: AMA1, Apical Membrane Antigen 1; GIA, growth inhibition assay; MSP1, Merozoite Surface Protein 1; CF, conversion factor; ANCOVA, analysis of covariance; CI, confidence interval.
This article has been cited by other articles:
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  K. Miura, H. Zhou, A. Diouf, S. E. Moretz, M. P. Fay, L. H. Miller, L. B. Martin, M. A. Pierce, R. D. Ellis, G. E. D. Mullen, et al. Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting Plasmodium falciparum Growth, as Determined by the In Vitro Growth Inhibition Assay Clin. Vaccine Immunol., July 1, 2009; 16(7): 963 - 968. [Abstract] [Full Text] [PDF]
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