Author | Medeiros, Camila Maia Pantuzzo | |
Author | Moreira, Eduardo Utsch Madureira | |
Author | Pires, Camilla Valente | |
Author | Torres, Leticia de Menezes | |
Author | Guimarães, Luiz Felipe Ferreira | |
Author | Alves, Jéssica Rafaela dos Santos | |
Author | Lima, Barbara Andreza Soares | |
Author | Fontes, Cor Jesus Fernandes | |
Author | Costa, Helena Lott | |
Author | Brito, Cristiana Ferreira Alves de | |
Author | Sousa, Tais Nobrega de | |
Author | Ntumngia, Francis B. | |
Author | Adams, John H. | |
Author | Kano, Flora Satiko | |
Author | Carvalho, Luzia Helena de | |
Access date | 2020-06-18T15:37:36Z | |
Available date | 2020-06-18T15:37:36Z | |
Document date | 2020 | |
Citation | MEDEIROS, Camila Maia Pantuzzo et al. Dynamics of IgM and IgG responses to the next generation of engineered Duffy binding protein II immunogen: Strain-specific and strain-transcending immune responses over a nine-year period. PLoS One, v. 15, n. 5, e0232786, 2020. | pt_BR |
ISSN | 1932-6203 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/41719 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Title | Dynamics of IgM and IgG responses to the next generation of engineered Duffy binding protein II immunogen: Strain-specific and strain-transcending immune responses over a nine-year period | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pone.0232786 | |
Abstract | Background: A low proportion of P. vivax-exposed individuals acquire protective strain-transcending neutralizing IgG antibodies that are able to block the interaction between the Duffy binding protein II (DBPII) and its erythrocyte-specific invasion receptor. In a recent study, a novel surface-engineered DBPII-based vaccine termed DEKnull-2, whose antibody response target conserved DBPII epitopes, was able to induce broadly binding-inhibitory IgG antibodies (BIAbs) that inhibit P. vivax reticulocyte invasion. Toward the development of DEKnull-2 as an effective P. vivax blood-stage vaccine, we investigate the relationship between naturally acquired DBPII-specific IgM response and the profile of IgG antibodies/BIAbs activity over time.
Methodology/principal findings: A nine-year follow-up study was carried-out among long-term P. vivax-exposed Amazonian individuals and included six cross-sectional surveys at periods of high and low malaria transmission. DBPII immune responses associated with either strain-specific (Sal1, natural DBPII variant circulating in the study area) or conserved epitopes (DEKnull-2) were monitored by conventional serology (ELISA-detected IgM and IgG antibodies), with IgG BIAbs activity evaluated by functional assays (in vitro inhibition of DBPII-erythrocyte binding). The results showed a tendency of IgM antibodies toward Sal1-specific response; the profile of Sal1 over DEKnull-2 was not associated with acute malaria and sustained throughout the observation period. The low malaria incidence in two consecutive years allowed us to demonstrate that variant-specific IgG (but not IgM) antibodies waned over time, which resulted in IgG skewed to the DEKnull-2 response. A persistent DBPII-specific IgM response was not associated with the presence (or absence) of broadly neutralizing IgG antibody response.
Conclusions/significance: The current study demonstrates that long-term exposure to low and unstable levels of P. vivax transmission led to a sustained DBPII-specific IgM response against variant-specific epitopes, while sustained IgG responses are skewed to conserved epitopes. Further studies should investigate on the role of a stable and persistent IgM antibody response in the immune response mediated by DBPII. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Mato Grosso. Hospital Júlio Muller. Cuiabá, MT, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida.Tampa, FL, United States of America. | pt_BR |
Affilliation | Center for Global Health and Infectious Diseases Research. College of Public Health. University of South Florida.Tampa, FL, United States of America. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. | pt_BR |
Subject | malaria | pt_BR |
Subject | Plasmodium vivax | pt_BR |