Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/27097
Title: Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites: Naturally Acquired Humoral Immune Response and B-Cell Epitope Mapping in Brazilian Amazon Inhabitants
Authors: Silva, Rodrigo Nunes Rodrigues da
Soares, Isabela Ferreira
Lopez-Camacho, Cesar
Silva, João Hermínio Martins da
Silva, Daiana de Souza Perce da
Têva, Antônio
Franco, Antônia Maria Ramos
Pinheiro, Francimeire Gomes
Chaves, Lana Bitencourt
Pratt-Riccio, Lilian Rose
Reyes-Sandoval, Arturo
Banic, Dalma Maria
Lima Junior, Josué da Costa
Affilliation: 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.
University of Oxford. The Henry Wellcome Building for Molecular Physiology. The Jenner Institute. Nuffield Department of Medicine. Oxford, UK.
Fundação Oswaldo Cruz. Grupo de Modelagem Computacional. Fortaleza, CE, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Ciências Biológicas. Laboratório de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Leishmanioses e Doença de Chagas. Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Leishmanioses e Doença de Chagas. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ. Brasil.
University of Oxford. The Henry Wellcome Building for Molecular Physiology. The Jenner Institute. Nuffield Department of Medicine. Oxford, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.
Abstract: The cell-traversal protein for ookinetes and sporozoites (CelTOS), a highly conserved antigen involved in sporozoite motility, plays an important role in the traversal of host cells during the preerythrocytic stage of Plasmodium species. Recently, it has been considered an alternative target when designing novel antimalarial vaccines against Plasmodium falciparum. However, the potential of Plasmodium vivax CelTOS as a vaccine target is yet to be explored. This study evaluated the naturally acquired immune response against a recombinant P. vivax CelTOS (PvCelTOS) (IgG and IgG subclass) in 528 individuals from Brazilian Amazon, as well as the screening of B-cell epitopes in silico and peptide assays to associate the breadth of antibody responses of those individuals with exposition and/or protection correlates. We show that PvCelTOS is naturally immunogenic in Amazon inhabitants with 94 individuals (17.8%) showing specific IgG antibodies against the recombinant protein. Among responders, the IgG reactivity indexes (RIs) presented a direct correlation with the number of previous malaria episodes (p = 0.003; r = 0.315) and inverse correlation with the time elapsed from the last malaria episode (p = 0.031; r = -0.258). Interestingly, high responders to PvCelTOS (RI > 2) presented higher number of previous malaria episodes, frequency of recent malaria episodes, and ratio of cytophilic/non-cytophilic antibodies than low responders (RI < 2) and non-responders (RI < 1). Moreover, a high prevalence of the cytophilic antibody IgG1 over all other IgG subclasses (p < 0.0001) was observed. B-cell epitope mapping revealed five immunogenic regions in PvCelTOS, but no associations between the specific IgG response to peptides and exposure/protection parameters were found. However, the epitope (PvCelTOSI136-E143) was validated as a main linear B-cell epitope, as 92% of IgG responders to PvCelTOS were also responders to this peptide sequence. This study describes for the first time the natural immunogenicity of PvCelTOS in Amazon individuals and identifies immunogenic regions in a full-length protein. The IgG magnitude was mainly composed of cytophilic antibodies (IgG1) and associated with recent malaria episodes. The data presented in this paper add further evidence to consider PvCelTOS as a vaccine candidate.
Keywords: PvCelTOS
P. vivax
vaccines
epitope mapping
epitope prediction
malaria vaccines
malaria
keywords: Malária
Vacinas
Plasmodium vivax
mapeamento de epitopos
previsão de epítopo
Amazônia Brasileira
Issue Date: 2017
Publisher: Frontiers Media
Citation: SILVA, Rodrigo Nunes Rodrigues da; et al. Plasmodium vivax cell-Traversal Protein for Ookinetes and sporozoites: naturally acquired humoral immune response and B-cell epitope Mapping in Brazilian amazon inhabitants. Frontiers in Immunology, v.8, Article 77, 13p, Feb. 2017.
DOI: 10.3389/fimmu.2017.00077
ISSN: 1664-3224
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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