PMID- 21713006 OWN - NLM STAT- MEDLINE DCOM- 20111121 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 6 DP - 2011 TI - Identification of a highly antigenic linear B cell epitope within Plasmodium vivax apical membrane antigen 1 (AMA-1). PG - e21289 LID - 10.1371/journal.pone.0021289 [doi] LID - e21289 AB - Apical membrane antigen 1 (AMA-1) is considered to be a major candidate antigen for a malaria vaccine. Previous immunoepidemiological studies of naturally acquired immunity to Plasmodium vivax AMA-1 (PvAMA-1) have shown a higher prevalence of specific antibodies to domain II (DII) of AMA-1. In the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length AMA-1 and DII. Also, we demonstrated a strong association between AMA-1 and DII IgG and IgG subclass responses. We analyzed the primary sequence of PvAMA-1 for B cell linear epitopes co-occurring with intrinsically unstructured/disordered regions (IURs). The B cell epitope comprising the amino acid sequence 290-307 of PvAMA-1 (SASDQPTQYEEEMTDYQK), with the highest prediction scores, was identified in domain II and further selected for chemical synthesis and immunological testing. The antigenicity of the synthetic peptide was identified by serological analysis using sera from P. vivax-infected individuals who were knowingly reactive to the PvAMA-1 ectodomain only, domain II only, or reactive to both antigens. Although the synthetic peptide was recognized by all serum samples specific to domain II, serum with reactivity only to the full-length protein presented 58.3% positivity. Moreover, IgG reactivity against PvAMA-1 and domain II after depletion of specific synthetic peptide antibodies was reduced by 18% and 33% (P = 0.0001 for both), respectively. These results suggest that the linear epitope SASDQPTQYEEEMTDYQK is highly antigenic during natural human infections and is an important antigenic region of the domain II of PvAMA-1, suggesting its possible future use in pre-clinical studies. FAU - Bueno, Lilian Lacerda AU - Bueno LL AD - Departamento de Parasitologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Lobo, Francisco Pereira AU - Lobo FP FAU - Morais, Cristiane Guimaraes AU - Morais CG FAU - Mourao, Luiza Carvalho AU - Mourao LC FAU - de Avila, Ricardo Andrez Machado AU - de Avila RA FAU - Soares, Irene Silva AU - Soares IS FAU - Fontes, Cor Jesus AU - Fontes CJ FAU - Lacerda, Marcus Vinicius AU - Lacerda MV FAU - Chavez Olortegui, Carlos AU - Chavez Olortegui C FAU - Bartholomeu, Daniella Castanheira AU - Bartholomeu DC FAU - Fujiwara, Ricardo Toshio AU - Fujiwara RT FAU - Braga, Erika Martins AU - Braga EM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110621 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibodies, Protozoan) RN - 0 (Antigens, Protozoan) RN - 0 (Epitopes, B-Lymphocyte) RN - 0 (Membrane Proteins) RN - 0 (Peptides) RN - 0 (Protozoan Proteins) RN - 0 (apical membrane antigen I, Plasmodium) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Amino Acid Sequence MH - Animals MH - Antibodies, Protozoan/blood/genetics/immunology MH - Antigens, Protozoan/genetics/*immunology MH - Epitopes, B-Lymphocyte/*immunology MH - Humans MH - Malaria, Vivax/blood/immunology/microbiology MH - Membrane Proteins/genetics/*immunology MH - Middle Aged MH - Molecular Sequence Data MH - Peptides/genetics/immunology MH - Plasmodium vivax/cytology/*immunology MH - Protozoan Proteins/genetics/*immunology MH - Young Adult PMC - PMC3119695 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/06/30 06:00 MHDA- 2011/12/13 00:00 PMCR- 2011/06/21 CRDT- 2011/06/30 06:00 PHST- 2010/12/21 00:00 [received] PHST- 2011/05/25 00:00 [accepted] PHST- 2011/06/30 06:00 [entrez] PHST- 2011/06/30 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2011/06/21 00:00 [pmc-release] AID - PONE-D-11-00265 [pii] AID - 10.1371/journal.pone.0021289 [doi] PST - ppublish SO - PLoS One. 2011;6(6):e21289. doi: 10.1371/journal.pone.0021289. Epub 2011 Jun 21.