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https://www.arca.fiocruz.br/handle/icict/56622
ANTIBODY RESPONSE TO A NEW MEMBER OF THE DBL FAMILY (EBP2) AFTER A BRIEF PLASMODIUM VIVAX EXPOSURE
Author
Lima, Bárbara Andreza Soares
Fernandes, Gabriela Maria
Torres, Letícia de Menezes
Pires, Camilla Valente
Alves, Jéssica Rafaela dos Santos
Nascimento, Sâmick Layene Moreira
Nascimento, Maria Fernanda Alves do
Afonso, Sofia Lara
Costa, Helena Lofft
Cerávolo, Isabela Penna
Sousa, Tais Nobrega
Soares, Irene S
Ntumngia, Francis Babila
Adams, John H
Carvalho, Luzia Helena
Kano, Flora Satiko
Fernandes, Gabriela Maria
Torres, Letícia de Menezes
Pires, Camilla Valente
Alves, Jéssica Rafaela dos Santos
Nascimento, Sâmick Layene Moreira
Nascimento, Maria Fernanda Alves do
Afonso, Sofia Lara
Costa, Helena Lofft
Cerávolo, Isabela Penna
Sousa, Tais Nobrega
Soares, Irene S
Ntumngia, Francis Babila
Adams, John H
Carvalho, Luzia Helena
Kano, Flora Satiko
Affilliation
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida. Tampa, Florida, United States of America.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas. São Paulo, SP, Brazil.
Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida. Tampa, Florida, United States of America.
Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida. Tampa, Florida, United States of America.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida. Tampa, Florida, United States of America.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas. São Paulo, SP, Brazil.
Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida. Tampa, Florida, United States of America.
Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida. Tampa, Florida, United States of America.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brazil.
Abstract
Plasmodium vivax blood-stage invasion into reticulocyte is critical for parasite development. Thus, validation of novel parasite invasion ligands is essential for malaria vaccine development. Recently, we demonstrated that EBP2, a Duffy binding protein (DBP) paralog, is antigenically distinct from DBP and could not be functionally inhibited by anti-DBP antibodies. Here, we took advantage of a small outbreak of P.vivax malaria, located in a non-malarious area of Brazil, to investigate for the first time IgM/IgG antibodies against EBP2 and DEKnull-2 (an engineering DBPII vaccine) among individuals who had their first and brief exposure to P.vivax (16 cases and 22 non-cases). Our experimental approach included 4 cross sectional surveys at 3-month interval (12-month follow-up). The results demonstrated that while a brief initial P.vivax infection was not efficient to induce IgM/ IgG antibodies to either EBP2 or DEKnull-2, IgG antibodies against DEKnull-2 (but not EBP2) were boosted by recurrent blood-stage infections following treatment. Of interest, in most recurrent P. vivax infections (4 out of 6 patients) DEKnull-2 IgG antibodies were sustained for 6 to 12 months. Polymorphisms in the ebp2 gene does not seem to explain EBP2 low immunogenicity as the ebp2 allele associated with the P.vivax outbreak presented high identity to the original EBP2 isolate used as recombinant protein. Although EBP2 antibodies were barely detectable after a primary episode of P.vivax infection, EBP2 was highly recognized by serum IgG from long-term malaria-exposed Amazonians (range from 35 to 92% according to previous malaria episodes). Taken together, the results showed that individuals with a single and brief exposure to P.vivax infection develop very low anti-EBP2 antibodies, which tend to increase after long-term malaria exposure. Finally, the findings highlighted the potential of DEKnull-2 as a vaccine candidate, as in non-immune individuals anti-DEKnull-2 IgG antibodies were boosted even after a brief exposure to P.vivax blood stages.
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