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.

<h4>Background</h4>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...

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Main Authors: Luiz F F Guimarães, Bárbara A Rodrigues, Michelle H F Dias, Matheus G Barcelos, Maria F A Nascimento, Sâmick L Moreira-Nascimento, Sofia L Afonso, Barbara G S Abreu, Jaap M Middeldorp, Francis B Ntumngia, John H Adams, Camila Fabbri, Stefanie Lopes, Cor J F Fernandes, Flora S Kano, Luzia H Carvalho
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0311704
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author Luiz F F Guimarães
Bárbara A Rodrigues
Michelle H F Dias
Matheus G Barcelos
Maria F A Nascimento
Sâmick L Moreira-Nascimento
Sofia L Afonso
Barbara G S Abreu
Jaap M Middeldorp
Francis B Ntumngia
John H Adams
Camila Fabbri
Stefanie Lopes
Cor J F Fernandes
Flora S Kano
Luzia H Carvalho
author_facet Luiz F F Guimarães
Bárbara A Rodrigues
Michelle H F Dias
Matheus G Barcelos
Maria F A Nascimento
Sâmick L Moreira-Nascimento
Sofia L Afonso
Barbara G S Abreu
Jaap M Middeldorp
Francis B Ntumngia
John H Adams
Camila Fabbri
Stefanie Lopes
Cor J F Fernandes
Flora S Kano
Luzia H Carvalho
author_sort Luiz F F Guimarães
collection DOAJ
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 correlation between malaria infection and EBV-DNAemia.<h4>Conclusions/significance</h4>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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language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-ee02b996c0d4407e9bb6f1c72b19eef52025-02-05T05:31:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031170410.1371/journal.pone.0311704Antibody response to Plasmodium vivax in the context of Epstein-Barr virus (EBV) co-infection: A 14-year follow-up study in the Amazon rainforest.Luiz F F GuimarãesBárbara A RodriguesMichelle H F DiasMatheus G BarcelosMaria F A NascimentoSâmick L Moreira-NascimentoSofia L AfonsoBarbara G S AbreuJaap M MiddeldorpFrancis B NtumngiaJohn H AdamsCamila FabbriStefanie LopesCor J F FernandesFlora S KanoLuzia H Carvalho<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 correlation between malaria infection and EBV-DNAemia.<h4>Conclusions/significance</h4>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.https://doi.org/10.1371/journal.pone.0311704
spellingShingle Luiz F F Guimarães
Bárbara A Rodrigues
Michelle H F Dias
Matheus G Barcelos
Maria F A Nascimento
Sâmick L Moreira-Nascimento
Sofia L Afonso
Barbara G S Abreu
Jaap M Middeldorp
Francis B Ntumngia
John H Adams
Camila Fabbri
Stefanie Lopes
Cor J F Fernandes
Flora S Kano
Luzia H Carvalho
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.
PLoS ONE
title 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_short 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.
title_sort 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
url https://doi.org/10.1371/journal.pone.0311704
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