Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/14428
Title: In silico Identification and Validation of a Linear and Naturally Immunogenic B-Cell Epitope of the Plasmodium vivax Malaria Vaccine Candidate Merozoite Surface Protein-9
Authors: Silva, Rodrigo Nunes Rodrigues da
Silva, João Hermínio Martins da
Singh, Balwan
Jiang, Jianlin
Meyer, Esmeralda V. S.
Santos, Fátima
Banic, Dalma Maria
Moreno, Alberto
Galinski, Mary R.
Ferreira, Joseli Oliveira
Lima Junior, Josué da Costa
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Grupo de Modelagem Computacional. Fortaleza, CE, Brasil.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA.
Emory University. Environmental Health and Safety Office. Atlanta, GA, USA.
Fundação Nacional de Saúde. Departamento de Entomologia. Laboratório central. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Referência Nacional de Simulídeos e Oncocercose. Rio de Janeiro, RJ, Brasil.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA / Emory University. Emory University School of Medicine. Department of Medicine. Division of Infectious Diseases. Atlanta, GA, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA / Emory University. Emory University School of Medicine. Department of Medicine. Division of Infectious Diseases. Atlanta, GA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Abstract: Synthetic peptide vaccines provide the advantages of safety, stability and low cost. The success of this approach is highly dependent on efficient epitope identification and synthetic strategies for efficacious delivery. In malaria, the Merozoite Surface Protein-9 of Plasmodium vivax (PvMSP9) has been considered a vaccine candidate based on the evidence that specific antibodies were able to inhibit merozoite invasion and recombinant proteins were highly immunogenic in mice and humans. However the identities of linear B-cell epitopes within PvMSP9 as targets of functional antibodies remain undefined. We used several publicly- available algorithms for in silico analyses and prediction of relevant B cell epitopes within PMSP9.We show that the tandem repeat sequence EAAPENAEPVHENA (PvMSP9E795-A808) present at the C-terminal region is a promising target for antibodies, given its high combined score to be a linear epitope and located in a putative intrinsically unstructured region of the native protein. To confirm the predictive value of the computational approach, plasma samples from 545 naturally exposed individuals were screened for IgG reactivity against the recombinant PvMSP9-RIRII729-972 and a synthetic peptide representing the predicted B cell epitope PvMSP9E795-A808. 316 individuals (58%) were responders to the full repetitive region PvMSP9-RIRII, of which 177 (56%) also presented total IgG reactivity against the synthetic peptide, confirming it validity as a B cell epitope. The reactivity indexes of anti-PvMSP9-RIRII and anti-PvMSP9E795-A808 antibodies were correlated. Interestingly, a potential role in the acquisition of protective immunity was associated with the linear epitope, since the IgG1 subclass against PvMSP9E795-A808 was the prevalent subclass and this directly correlated with time elapsed since the last malaria episode; however this was not observed in the antibody responses against the full PvMSP9-RIRII. In conclusion, our findings identified and experimentally confirmed the potential of PvMSP9E795-A808 as an immunogenic linear B cell epitope within the P. vivax malaria vaccine candidate PvMSP9 and support its inclusion in future subunit vaccines.
Keywords: Plasmodium vivax
Malaria
Vaccine
linear B cell epitope
Merozoite Surface Protein-9
keywords: Epitopo de célula linear B
Malária
Plasmodium vivax
Vacina
Proteína 9 de Superfície de Merozoito
Issue Date: 2016
Publisher: Public Library of Science
Citation: SILVA, Rodrigo Nunes Rodrigues da; et al. In silico Identification and Validation of a Linear and Naturally Immunogenic B-Cell Epitope of the Plasmodium vivax Malaria Vaccine Candidate Merozoite Surface Protein-9. Plos One, v.11, n.1, e0146951, 18p, Jan. 2016.
DOI: 10.1371/journal.pone.0146951
ISSN: 1932-6203
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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