Antibodies to Polymorphic Invasion-Inhibitory and Non-Inhibitory Epitopes of Plasmodium falciparum Apical Membrane Antigen 1 in Human Malaria
- Author(s)
- Mugyenyi, CK; Elliott, SR; McCallum, FJ; Anders, RF; Marsh, K; Beeson, JG;
- Details
- Publication Year 2013-07-05,Volume 8,Issue #7,Page e68304
- Journal Title
- PLOS ONE
- Publication Type
- Journal Article
- Abstract
- Background: Antibodies to P. falciparum apical membrane protein 1 (AMA1) may contribute to protective immunity against clinical malaria by inhibiting blood stage growth of P. falciparum, and AMA1 is a leading malaria vaccine candidate. Currently, there is limited knowledge of the acquisition of strain-specific and cross-reactive antibodies to AMA1 in humans, or the acquisition of invasion-inhibitory antibodies to AMA1. Methodology/Findings: We examined the acquisition of human antibodies to specific polymorphic invasion-inhibitory and non-inhibitory AMA1 epitopes, defined by the monoclonal antibodies 1F9 and 2C5, respectively. Naturally acquired antibodies were measured in cohorts of Kenyan children and adults. Antibodies to the invasion-inhibitory 1F9 epitope and non-inhibitory 2C5 epitope were measured indirectly by competition ELISA. Antibodies to the 1F9 and 2C5 epitopes were acquired by children and correlated with exposure, and higher antibody levels and prevalence were observed with increasing age and with active P. falciparum infection. Of note, the prevalence of antibodies to the inhibitory 1F9 epitope was lower than antibodies to AMA1 or the 2C5 epitope. Antibodies to AMA1 ectodomain, the 1F9 or 2C5 epitopes, or a combination of responses, showed some association with protection from P. falciparum malaria in a prospective longitudinal study. Furthermore, antibodies to the invasion-inhibitory 1F9 epitope were positively correlated with parasite growth-inhibitory activity of serum antibodies. Conclusions/Significance: Individuals acquire antibodies to functional, polymorphic epitopes of AMA1 that may contribute to protective immunity, and these findings have implications for AMA1 vaccine development. Measuring antibodies to the 1F9 epitope by competition ELISA may be a valuable approach to assessing human antibodies with invasion-inhibitory activity in studies of acquired immunity and vaccine trials of AMA1.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- VACCINE-CANDIDATE; CLINICAL MALARIA; ERYTHROCYTE INVASION; MEROZOITE ANTIGENS; IMMUNE-RESPONSES; KENYAN COAST; AMA1; PROTECTION; CHILDREN; TRANSMISSION
- Research Division(s)
- Infection And Immunity
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702562/
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0068304
- Open Access at Publisher's Site
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0068304- Terms of Use/Rights Notice
- Copyright: © 2013 Mugyenyi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creation Date: 2013-07-05 12:00:00