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ANTIBODY RESPONSE TO PLASMODIUM VIVAX IN THE CONTEXT OF EPSTEIN-BARR VIRUS (EBV) CO-INFECTION: A 14-YEAR FOLLOW-UP STUDY IN THE AMAZON RAINFOREST
Author
Guimarães, Luiz Felipe Ferreira
Rodrigues, Bárbara A.
Dias, Michelle Hallais França
Barcelos, Matheus Gomes
Nascimento, Maria Fernanda Alves do
Moreira -Nascimento, Sâmick Layene
Afonso, Sofia Lara
Abreu, Barbara G. S.
Middeldorp, Jaap. M.
Ntumngia, Francis B.
Adams, John H.
Fabbri, Camila
Lopes, Stefanie
Fontes, Cor Jesus Fernandes
Kano, Flora Satiko
Carvalho, Luzia Helena
Rodrigues, Bárbara A.
Dias, Michelle Hallais França
Barcelos, Matheus Gomes
Nascimento, Maria Fernanda Alves do
Moreira -Nascimento, Sâmick Layene
Afonso, Sofia Lara
Abreu, Barbara G. S.
Middeldorp, Jaap. M.
Ntumngia, Francis B.
Adams, John H.
Fabbri, Camila
Lopes, Stefanie
Fontes, Cor Jesus Fernandes
Kano, Flora Satiko
Carvalho, Luzia Helena
Affilliation
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de vírus. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus AM, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil /Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Unidade de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.
Vrije Universiteit Medical Center.Department of Pathology. Amsterdam, The Netherlands.
University of South Florida. College of Public Health.Center for Global Health and Interdisciplinary Disease Research. Tampa, Florida, United States.
Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus AM, Brazil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Unidade de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Unidade de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade Federal de Mato Grosso. Faculdade de Medicina. Hospital Universitário Julio Müller. Cuiabá, MT, Brasil.
Universidade Federal de Mato Grosso. Faculdade de Medicina. Hospital Universitário Julio Müller. Cuiabá, MT, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de vírus. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus AM, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil /Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Unidade de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.
Vrije Universiteit Medical Center.Department of Pathology. Amsterdam, The Netherlands.
University of South Florida. College of Public Health.Center for Global Health and Interdisciplinary Disease Research. Tampa, Florida, United States.
Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus AM, Brazil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Unidade de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Unidade de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade Federal de Mato Grosso. Faculdade de Medicina. Hospital Universitário Julio Müller. Cuiabá, MT, Brasil.
Universidade Federal de Mato Grosso. Faculdade de Medicina. Hospital Universitário Julio Müller. Cuiabá, MT, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Abstract
Background To develop an effective vaccine against Plasmodium vivax, the most widely dispersed human malaria parasite, it is critical to understand how coinfections with other pathogens could impact malaria-specific immune response. A recent conceptual study proposed that Epstein-Barr virus (EBV), a highly prevalent human herpesvirus that establishes lifelong persistent infection, may influence P. vivax antibody responses. Here, it was investigated whether EBV could impact the longevity of humoral immune response to P. vivax.
Methodology/principal findings A 14-year follow-up study was carried out among long-term P. vivax-exposed Amazonian individuals (272, median age 35 years), and included 9 cross-sectional surveys at periods of high and low malaria transmission. The experimental approach focused on monitoring antibodies to the major blood-stage P. vivax vaccine candidate, the Duffy binding protein region II (DBPII-Sal1), including a novel engineered DBPII-based vaccine targeting conserved epitopes (DEKnull-2). In parallel, the status of EBV infection was determined over time by the detection of circulating EBV DNA (EBV-DNAemia) and EBV-specific antibodies to lytic (VCAp18) or latent (EBNA1) antigens. Regardless of the malaria transmission period, the results demonstrated that one or multiple episodes of EBV-DNAemia did not influence the longevity of DBPII immune responses to both strain-specific (Sal-1) or strain-transcending (DEKnull-2) antibodies. Also, the average time in which DBPII-responders lost their antibodies was unrelated to the EBV serostatus. Considering all malaria cases detected during the study, there was a predominance of P. vivax mono-infection (76%), with a positive association between malaria infection and detectable EBV-DNAemia.
Conclusions/significance In an immunocompetent P. vivax-exposed adult population neither sporadic episodes of EBV-DNAemia nor antibody responses to lytic/latent EBV antigens influence the longevity of both strain-specific and strain-transcending DBPII immune responses. Further studies should investigate the role of acute P. vivax infection in the activation of EBV replication cycle.
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