Journal Article

Association between Naturally Acquired Antibodies to Erythrocyte-Binding Antigens of Plasmodium falciparum and Protection from Malaria and High-Density Parasitemia

Jack S. Richards, Danielle I. Stanisic, Freya J. I. Fowkes, Livingstone Tavul, Elijah Dabod, Jennifer K. Thompson, Sanjeev Kumar, Chetan E. Chitnis, David L. Narum, Pascal Michon, Peter M. Siba, Alan F. Cowman, Ivo Mueller and James G. Beeson

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 8, pages e50-e60
Published in print October 2010 | ISSN: 1058-4838
Published online October 2010 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/656413
Association between Naturally Acquired Antibodies to Erythrocyte-Binding Antigens of Plasmodium falciparum and Protection from Malaria and High-Density Parasitemia

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Background. Antibodies targeting blood stage antigens are important in protection against malaria, but the principle targets remain unclear. Erythrocyte-binding antigens (EBAs) are important erythrocyte invasion ligands used by merozoites and may be targets of protective immunity, but there are limited data examining their potential importance.

Methods. We examined antibodies among 206 Papua New Guinean children who were treated with antimalarials at enrolment and observed prospectively for 6 months for reinfection and malaria. Immunoglobulin (Ig) G, IgG subclasses, and IgM to different regions of EBA175, EBA140, and EBA181 expressed as recombinant proteins were assessed in comparison with several other merozoite antigens.

Results. High levels of IgG to each of the EBAs were strongly associated with protection from symptomatic malaria and high density parasitemia, but not with risk of reinfection per se. The predominant IgG subclasses were either IgG1 or IgG3, depending on the antigen. The predominance of IgG1 versus IgG3 reflected structural features of specific regions of the proteins. IgG3 was most strongly associated with protection, even for those antigens that had an IgG1 predominant response.

Conclusions. The EBAs appear important targets of acquired protective immunity. These findings support their further development as vaccine candidates.

Journal Article.  5160 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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