The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile
Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective antimalarial vaccine is still urgently needed. P. vivax vaccine development involve...
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| Formato: | Artículo (Article) |
| Lenguaje: | Inglés (English) |
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Frontiers Media S.A.
2018
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| Acceso en línea: | https://repository.urosario.edu.co/handle/10336/24079 https://doi.org/10.3389/fcimb.2018.00156 |
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ir-10336-240792022-05-02T12:37:14Z The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile López, Carolina Yepes-Pérez, Yoelis Patarroyo, Manuel E. Patarroyo, Manuel A. Díaz Arévalo, Diana Alkaline phosphatase Epitope Gamma interferon Hla drb1 antigen Interleukin 10 Interleukin 6 Plasmodium vivax rhoptry neck protein 2 Protein Streptavidin Tumor necrosis factor Unclassified drug Cytokine Epitope Hla drb1 antigen Immunoglobulin g Parasite antigen Peptide Protozoal protein Antigenicity Article Bioinformatics Cell isolation Cell proliferation Cytokine release Enzyme linked immunospot assay Human Human cell Humoral immunity Ic50 Immune response Immunofluorescence Peripheral blood mononuclear cell Plasmodium vivax Western blotting Biology Blood Colombia Immunology Metabolism Plasmodium falciparum Plasmodium vivax Plasmodium vivax malaria Cell proliferation Colombia Computational biology Cytokines Hla-drb1 chains Humans Immunoglobulin g Inhibitory concentration 50 Interferon-gamma Interleukin-10 Interleukin-6 Peptides Plasmodium falciparum Plasmodium vivax Protozoan proteins Antigenicity Cellular and humoral response Epitope Hla-drb1 typing Plasmodium vivax Pvron2 Synthetic peptide b-lymphocyte humoral protozoan t-lymphocyte vivax Antigens Epitopes Epitopes Immunity Malaria Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective antimalarial vaccine is still urgently needed. P. vivax vaccine development involves analyzing naturally-infected patients' immune response to the specific proteins involved in red blood cell invasion. The P. vivax rhoptry neck protein 2 (PvRON2) is a highly conserved protein which is expressed in late schizont rhoptries; it interacts directly with AMA-1 and might be involved in moving-junction formation. Bioinformatics approaches were used here to select B- and T-cell epitopes. Eleven high-affinity binding peptides were selected using the NetMHCIIpan-3.0 in silico prediction tool; their in vitro binding to HLA-DRB1*0401, HLA-DRB1*0701, HLA-DRB1*1101 or HLA-DRB1*1302 was experimentally assessed. Four peptides (39152 (HLA-DRB1*04 and 11), 39047 (HLA-DRB1*07), 39154 (HLADRB1*13) and universal peptide 39153) evoked a naturally-acquired T-cell immune response in P. vivax-exposed individuals from two endemic areas in Colombia. All four peptides had an SI greater than 2 in proliferation assays; however, only peptides 39154 and 39153 had significant differences compared to the control group. Peptide 39047 was able to significantly stimulate TNF and IL-10 production while 39154 stimulated TNF production. Allele-specific peptides (but not the universal one) were able to stimulate IL-6 production; however, none induced IFN-? production. The Bepipred 1.0 tool was used for selecting four B-cell epitopes in silico regarding humoral response. Peptide 39041 was the only one recognized by P. vivax-exposed individuals' sera and had significant differences concerning IgG subclasses; an IgG2 > IgG4 profile was observed for this peptide, agreeing with a protection-inducing role against P. falciparum and P. vivax as previously described for antigens such as RESA and MSP2. The bioinformatics results and in vitro evaluation reported here highlighted two T-cell epitopes (39047 and 39154) being recognized by memory cells and a B-cell epitope (39041) identified by P. vivax-exposed individuals' sera which could be used as potential candidates when designing a subunit-based vaccine. © 2018 López, Yepes-Pérez, Díaz-Arévalo, Patarroyo and Patarroyo. 2018 2020-05-26T00:08:21Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 22352988 https://repository.urosario.edu.co/handle/10336/24079 https://doi.org/10.3389/fcimb.2018.00156 eng info:eu-repo/semantics/openAccess application/pdf Frontiers Media S.A. instname:Universidad del Rosario |
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EdocUR - Universidad del Rosario |
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DSpace |
| language |
Inglés (English) |
| topic |
Alkaline phosphatase Epitope Gamma interferon Hla drb1 antigen Interleukin 10 Interleukin 6 Plasmodium vivax rhoptry neck protein 2 Protein Streptavidin Tumor necrosis factor Unclassified drug Cytokine Epitope Hla drb1 antigen Immunoglobulin g Parasite antigen Peptide Protozoal protein Antigenicity Article Bioinformatics Cell isolation Cell proliferation Cytokine release Enzyme linked immunospot assay Human Human cell Humoral immunity Ic50 Immune response Immunofluorescence Peripheral blood mononuclear cell Plasmodium vivax Western blotting Biology Blood Colombia Immunology Metabolism Plasmodium falciparum Plasmodium vivax Plasmodium vivax malaria Cell proliferation Colombia Computational biology Cytokines Hla-drb1 chains Humans Immunoglobulin g Inhibitory concentration 50 Interferon-gamma Interleukin-10 Interleukin-6 Peptides Plasmodium falciparum Plasmodium vivax Protozoan proteins Antigenicity Cellular and humoral response Epitope Hla-drb1 typing Plasmodium vivax Pvron2 Synthetic peptide b-lymphocyte humoral protozoan t-lymphocyte vivax Antigens Epitopes Epitopes Immunity Malaria |
| spellingShingle |
Alkaline phosphatase Epitope Gamma interferon Hla drb1 antigen Interleukin 10 Interleukin 6 Plasmodium vivax rhoptry neck protein 2 Protein Streptavidin Tumor necrosis factor Unclassified drug Cytokine Epitope Hla drb1 antigen Immunoglobulin g Parasite antigen Peptide Protozoal protein Antigenicity Article Bioinformatics Cell isolation Cell proliferation Cytokine release Enzyme linked immunospot assay Human Human cell Humoral immunity Ic50 Immune response Immunofluorescence Peripheral blood mononuclear cell Plasmodium vivax Western blotting Biology Blood Colombia Immunology Metabolism Plasmodium falciparum Plasmodium vivax Plasmodium vivax malaria Cell proliferation Colombia Computational biology Cytokines Hla-drb1 chains Humans Immunoglobulin g Inhibitory concentration 50 Interferon-gamma Interleukin-10 Interleukin-6 Peptides Plasmodium falciparum Plasmodium vivax Protozoan proteins Antigenicity Cellular and humoral response Epitope Hla-drb1 typing Plasmodium vivax Pvron2 Synthetic peptide b-lymphocyte humoral protozoan t-lymphocyte vivax Antigens Epitopes Epitopes Immunity Malaria López, Carolina Yepes-Pérez, Yoelis Patarroyo, Manuel E. Patarroyo, Manuel A. Díaz Arévalo, Diana The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile |
| description |
Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective antimalarial vaccine is still urgently needed. P. vivax vaccine development involves analyzing naturally-infected patients' immune response to the specific proteins involved in red blood cell invasion. The P. vivax rhoptry neck protein 2 (PvRON2) is a highly conserved protein which is expressed in late schizont rhoptries; it interacts directly with AMA-1 and might be involved in moving-junction formation. Bioinformatics approaches were used here to select B- and T-cell epitopes. Eleven high-affinity binding peptides were selected using the NetMHCIIpan-3.0 in silico prediction tool; their in vitro binding to HLA-DRB1*0401, HLA-DRB1*0701, HLA-DRB1*1101 or HLA-DRB1*1302 was experimentally assessed. Four peptides (39152 (HLA-DRB1*04 and 11), 39047 (HLA-DRB1*07), 39154 (HLADRB1*13) and universal peptide 39153) evoked a naturally-acquired T-cell immune response in P. vivax-exposed individuals from two endemic areas in Colombia. All four peptides had an SI greater than 2 in proliferation assays; however, only peptides 39154 and 39153 had significant differences compared to the control group. Peptide 39047 was able to significantly stimulate TNF and IL-10 production while 39154 stimulated TNF production. Allele-specific peptides (but not the universal one) were able to stimulate IL-6 production; however, none induced IFN-? production. The Bepipred 1.0 tool was used for selecting four B-cell epitopes in silico regarding humoral response. Peptide 39041 was the only one recognized by P. vivax-exposed individuals' sera and had significant differences concerning IgG subclasses; an IgG2 > IgG4 profile was observed for this peptide, agreeing with a protection-inducing role against P. falciparum and P. vivax as previously described for antigens such as RESA and MSP2. The bioinformatics results and in vitro evaluation reported here highlighted two T-cell epitopes (39047 and 39154) being recognized by memory cells and a B-cell epitope (39041) identified by P. vivax-exposed individuals' sera which could be used as potential candidates when designing a subunit-based vaccine. © 2018 López, Yepes-Pérez, Díaz-Arévalo, Patarroyo and Patarroyo. |
| format |
Artículo (Article) |
| author |
López, Carolina Yepes-Pérez, Yoelis Patarroyo, Manuel E. Patarroyo, Manuel A. Díaz Arévalo, Diana |
| author_facet |
López, Carolina Yepes-Pérez, Yoelis Patarroyo, Manuel E. Patarroyo, Manuel A. Díaz Arévalo, Diana |
| author_sort |
López, Carolina |
| title |
The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile |
| title_short |
The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile |
| title_full |
The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile |
| title_fullStr |
The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile |
| title_full_unstemmed |
The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile |
| title_sort |
in vitro antigenicity of plasmodium vivax rhoptry neck protein 2 (pvron2) b- and t-epitopes selected by hla-drb1 binding profile |
| publisher |
Frontiers Media S.A. |
| publishDate |
2018 |
| url |
https://repository.urosario.edu.co/handle/10336/24079 https://doi.org/10.3389/fcimb.2018.00156 |
| _version_ |
1740172541986603008 |
| score |
12,131701 |