Identification of a highly antigenic linear B cell epitope within Plasmodium vivax apical membrane antigen 1 (AMA-1)

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 p...

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Published in:PloS one 2011-06, Vol.6 (6), p.e21289-e21289
Main Authors: Bueno, Lilian Lacerda, Lobo, Francisco Pereira, Morais, Cristiane Guimarães, Mourão, Luíza Carvalho, de Ávila, Ricardo Andrez Machado, Soares, Irene Silva, Fontes, Cor Jesus, Lacerda, Marcus Vinícius, Chavez Olórtegui, Carlos, Bartholomeu, Daniella Castanheira, Fujiwara, Ricardo Toshio, Braga, Erika Martins
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Amino Acid Sequence
Amino acids
Analysis
Animals
Antibodies
Antibodies, Protozoan - blood
Antibodies, Protozoan - genetics
Antibodies, Protozoan - immunology
Antigenic determinants
Antigenicity
Antigens
Antigens, Protozoan - genetics
Antigens, Protozoan - immunology
Apical membrane antigen 1
Apicomplexa
Biology
Blood & organ donations
Chemical synthesis
Echinococcus
Epitopes
Epitopes, B-Lymphocyte - immunology
Erythrocytes
Genomics
Humans
Immunity
Immunoglobulin G
Immunology
Infections
Lymphocytes B
Malaria
Malaria vaccines
Malaria, Vivax - blood
Malaria, Vivax - immunology
Malaria, Vivax - microbiology
Medical research
Medical societies
Medicine
Membrane Proteins - genetics
Membrane Proteins - immunology
Microscopy
Middle Aged
Molecular Sequence Data
Parasites
Parasitic diseases
Peptides
Peptides - genetics
Peptides - immunology
Plasmodium
Plasmodium falciparum
Plasmodium vivax
Plasmodium vivax - cytology
Plasmodium vivax - immunology
Proteins
Protozoan Proteins - genetics
Protozoan Proteins - immunology
Vaccines
Vector-borne diseases
Young Adult
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0021289