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Infection and Immunity, December 2007, p. 5827-5836, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00593-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Immunization with Plasmodium falciparum Apical Membrane Antigen 1, the Specificity of Antibodies Depends on the Species Immunized ^,

Kazutoyo Miura,^* Hong Zhou, Olga V. Muratova, Andrew C. Orcutt, Birgitte Giersing, Louis H. Miller, and Carole A. Long

Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland

Received 25 April 2007/ Returned for modification 18 June 2007/ Accepted 26 September 2007

At least a million people, mainly African children under 5 years old, still die yearly from malaria, and the burden of disease and death has increased. Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is one of the most promising blood-stage malarial vaccine candidates. However, the allelic polymorphism observed in this protein is a potential stumbling block for vaccine development. To overcome the polymorphism- and strain-specific growth inhibition in vitro, we previously showed in a rabbit model that vaccination with a mixture of two allelic forms of PfAMA1 induced parasite growth-inhibitory antisera against both strains of P. falciparum parasites in vitro. In the present study, we have established that, in contrast to a single-allele protein, the antigen mixture elicits primarily antibodies recognizing antigenic determinants common to the two antigens, as judged by an antigen reversal growth inhibition assay (GIA). We also show that a similar reactivity pattern occurs after immunization of mice. By contrast, sera from rhesus monkeys do not distinguish the two alleles when tested by an enzyme-linked immunosorbent assay or by GIA, regardless of whether the immunogen is a single AMA1 protein or the mixture. This is the first report that a malarial vaccine candidate induced different specificities of functional antibodies depending on the animal species immunized. These observations, as well as data available on human immune responses in areas of endemicity, suggest that polymorphism in the AMA1 protein may not be as formidable a problem for vaccine development as anticipated from studies with rabbits and mice.

Published ahead of print on 8 October 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. F. Urban, Jr.

Present address: Malaria Vaccine Initiative, PATH, 7500 Old Georgetown Road, 12th Floor, Bethesda, MD 20814.

Present address: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Twinbrook 3, Room 3W-13, Rockville, MD 20852.