Humoral Immune Responses to a Single Allele PfAMA1 Vaccine in Healthy Malaria-Naı̈ve Adults

Plasmodium falciparum: apical membrane antigen 1 (AMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 mg) of a single allele AMA1 antigen (FVO) formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naı̈ve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i) Antibody responses to various allelic variants, (ii) Domain specificity, (iii) Avidity, (iv) IgG subclass levels, by ELISA and (v) functionality of antibody responses by Growth Inhibition Assay (GIA). About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains. Trial Registration: ClinicalTrials.gov NCT00730782 Citation: Remarque EJ, Roestenberg M, Younis S, Walraven V, van der Werff N, et al. (2012) Humoral Immune Responses to a Single Allele PfAMA1 Vaccine in Healthy Malaria-Naı̈ve Adults. PLoS ONE 7(6): e38898. doi:10.1371/journal.pone.0038898 Editor: James G. Beeson, Burnet Institute, Australia Received January 16, 2012; Accepted May 14, 2012; Published June 29, 2012 Copyright: 2012 Remarque 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. Funding: This work was funded by a grant from the European Malaria Vaccine Initiative. Collaborators from the European Malaria Vaccine Initiative have been involved in the study design, data collection and analysis, decision to publish and preparation of the manuscript. Competing Interests: Four of the authors (EJR, AWT, BWF and CHMK) are in the process of obtaining a patent for three synthetic Diversity-Covering (DiCo) PfAMA1 proteins. The authors wish to thank GlaxoSmithKline, Rixensart, Belgium, for supplying AS02 and SEPPIC, Paris, France, for supplying Montanide ISA 720. This does not alter their adherence to all the PLoS policies on sharing data and materials. * E-mail: [email protected]