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Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure

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 D...

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Autores principales: Lima, Bárbara A. S., Fernandes, Gabriela M., Torres, Letícia M., Pires, Camilla V., Alves, Jéssica R. S., Moreira-Nascimento, Sâmick L., Nascimento, Maria Fernanda A., Afonso, Sofia L., Costa, Helena L., Cerávolo, Isabela P., Sousa, Tais N., Soares, Irene S., Ntumngia, Francis B., Adams, John H., Carvalho, Luzia H., Kano, Flora S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205486/
https://www.ncbi.nlm.nih.gov/pubmed/35714097
http://dx.doi.org/10.1371/journal.pntd.0010493
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author Lima, Bárbara A. S.
Fernandes, Gabriela M.
Torres, Letícia M.
Pires, Camilla V.
Alves, Jéssica R. S.
Moreira-Nascimento, Sâmick L.
Nascimento, Maria Fernanda A.
Afonso, Sofia L.
Costa, Helena L.
Cerávolo, Isabela P.
Sousa, Tais N.
Soares, Irene S.
Ntumngia, Francis B.
Adams, John H.
Carvalho, Luzia H.
Kano, Flora S.
author_facet Lima, Bárbara A. S.
Fernandes, Gabriela M.
Torres, Letícia M.
Pires, Camilla V.
Alves, Jéssica R. S.
Moreira-Nascimento, Sâmick L.
Nascimento, Maria Fernanda A.
Afonso, Sofia L.
Costa, Helena L.
Cerávolo, Isabela P.
Sousa, Tais N.
Soares, Irene S.
Ntumngia, Francis B.
Adams, John H.
Carvalho, Luzia H.
Kano, Flora S.
author_sort Lima, Bárbara A. S.
collection PubMed
description 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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spelling pubmed-92054862022-06-18 Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure Lima, Bárbara A. S. Fernandes, Gabriela M. Torres, Letícia M. Pires, Camilla V. Alves, Jéssica R. S. Moreira-Nascimento, Sâmick L. Nascimento, Maria Fernanda A. Afonso, Sofia L. Costa, Helena L. Cerávolo, Isabela P. Sousa, Tais N. Soares, Irene S. Ntumngia, Francis B. Adams, John H. Carvalho, Luzia H. Kano, Flora S. PLoS Negl Trop Dis Research Article 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. Public Library of Science 2022-06-17 /pmc/articles/PMC9205486/ /pubmed/35714097 http://dx.doi.org/10.1371/journal.pntd.0010493 Text en © 2022 Lima et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lima, Bárbara A. S.
Fernandes, Gabriela M.
Torres, Letícia M.
Pires, Camilla V.
Alves, Jéssica R. S.
Moreira-Nascimento, Sâmick L.
Nascimento, Maria Fernanda A.
Afonso, Sofia L.
Costa, Helena L.
Cerávolo, Isabela P.
Sousa, Tais N.
Soares, Irene S.
Ntumngia, Francis B.
Adams, John H.
Carvalho, Luzia H.
Kano, Flora S.
Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure
title Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure
title_full Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure
title_fullStr Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure
title_full_unstemmed Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure
title_short Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure
title_sort antibody response to a new member of the dbl family (ebp2) after a brief plasmodium vivax exposure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205486/
https://www.ncbi.nlm.nih.gov/pubmed/35714097
http://dx.doi.org/10.1371/journal.pntd.0010493
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