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Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP

BACKGROUND: Immunological characterization of potential blood-stage malaria antigens would be a valuable strategy in the development of an effective vaccine. Identifying B and CD4(+) T cell epitopes will be important in understanding the nature of immune response. A previous study has shown that Pla...

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Autores principales: Kalra, Aakanksha, Mukherjee, Paushali, Chauhan, Virander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015194/
https://www.ncbi.nlm.nih.gov/pubmed/27604988
http://dx.doi.org/10.1186/s12936-016-1510-4
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author Kalra, Aakanksha
Mukherjee, Paushali
Chauhan, Virander S.
author_facet Kalra, Aakanksha
Mukherjee, Paushali
Chauhan, Virander S.
author_sort Kalra, Aakanksha
collection PubMed
description BACKGROUND: Immunological characterization of potential blood-stage malaria antigens would be a valuable strategy in the development of an effective vaccine. Identifying B and CD4(+) T cell epitopes will be important in understanding the nature of immune response. A previous study has shown that Plasmodium falciparum apical asparagine-rich protein (PfAARP) stimulates immune response and induces potent invasion-inhibitory antibodies. Antibodies to PfAARP provide synergistic effects in inhibition of parasite invasion when used in combination with antibodies to other antigens. In the present study, an attempt was made to identify B cell and CD4(+) T cell epitopes of PfAARP. METHODS: Balb/c mice were immunized with recombinant PfAARP and both cellular and humoral responses were analysed at various time points. Computerized databases [immune epitope database (IEDB) and B cell epitope prediction (BCEPred)] were used to predict epitope sequences within PfAARP and predicted peptides were synthesized. In addition, nine 18 amino acid, long-overlapping peptides spanning the entire length of PfAARP were synthesized. Using these peptides, B cell and CD4(+) T cell responses in PfAARP immunized mice were measured by ELISA and ELISPOT assays. RESULTS: Here, it is demonstrated that immunization of mice with PfAARP induced long-lasting, high-titre antibodies (4 months post immunization). Also, the recombinant protein was effective in inducing a pronounced Th1 type of immune response quantified by IFN-γ ELISA and ELISPOT. It was found that the predicted peptides did not represent the immunogenic regions of PfAARP. However, of the nine overlapping peptides, three peptides (peptides 3, 5 and 7) were strongly recognized by PfAARP-immunized sera and represented B cell epitopes. Also, peptide 3 elicited IFN- γ response, suggesting it to be a T-cell epitope. CONCLUSIONS: Induction of long-lasting humoral and cellular response on PfAARP immunization in mice underscores its possible use as a blood-stage malaria vaccine candidate. Mapping of immunogenic regions may help in designing fusion chimera containing immunologically relevant regions of other vaccine target antigens and/or for multi-component vaccine candidates.
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spelling pubmed-50151942016-09-09 Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP Kalra, Aakanksha Mukherjee, Paushali Chauhan, Virander S. Malar J Research BACKGROUND: Immunological characterization of potential blood-stage malaria antigens would be a valuable strategy in the development of an effective vaccine. Identifying B and CD4(+) T cell epitopes will be important in understanding the nature of immune response. A previous study has shown that Plasmodium falciparum apical asparagine-rich protein (PfAARP) stimulates immune response and induces potent invasion-inhibitory antibodies. Antibodies to PfAARP provide synergistic effects in inhibition of parasite invasion when used in combination with antibodies to other antigens. In the present study, an attempt was made to identify B cell and CD4(+) T cell epitopes of PfAARP. METHODS: Balb/c mice were immunized with recombinant PfAARP and both cellular and humoral responses were analysed at various time points. Computerized databases [immune epitope database (IEDB) and B cell epitope prediction (BCEPred)] were used to predict epitope sequences within PfAARP and predicted peptides were synthesized. In addition, nine 18 amino acid, long-overlapping peptides spanning the entire length of PfAARP were synthesized. Using these peptides, B cell and CD4(+) T cell responses in PfAARP immunized mice were measured by ELISA and ELISPOT assays. RESULTS: Here, it is demonstrated that immunization of mice with PfAARP induced long-lasting, high-titre antibodies (4 months post immunization). Also, the recombinant protein was effective in inducing a pronounced Th1 type of immune response quantified by IFN-γ ELISA and ELISPOT. It was found that the predicted peptides did not represent the immunogenic regions of PfAARP. However, of the nine overlapping peptides, three peptides (peptides 3, 5 and 7) were strongly recognized by PfAARP-immunized sera and represented B cell epitopes. Also, peptide 3 elicited IFN- γ response, suggesting it to be a T-cell epitope. CONCLUSIONS: Induction of long-lasting humoral and cellular response on PfAARP immunization in mice underscores its possible use as a blood-stage malaria vaccine candidate. Mapping of immunogenic regions may help in designing fusion chimera containing immunologically relevant regions of other vaccine target antigens and/or for multi-component vaccine candidates. BioMed Central 2016-09-07 /pmc/articles/PMC5015194/ /pubmed/27604988 http://dx.doi.org/10.1186/s12936-016-1510-4 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kalra, Aakanksha
Mukherjee, Paushali
Chauhan, Virander S.
Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP
title Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP
title_full Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP
title_fullStr Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP
title_full_unstemmed Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP
title_short Characterization of fine specificity of the immune response to a Plasmodium falciparum rhoptry neck protein, PfAARP
title_sort characterization of fine specificity of the immune response to a plasmodium falciparum rhoptry neck protein, pfaarp
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015194/
https://www.ncbi.nlm.nih.gov/pubmed/27604988
http://dx.doi.org/10.1186/s12936-016-1510-4
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