{"doi":"10.1371/journal.pone.0232786","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","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.","journal":"PLoS ONE","year":2020,"id":88165,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":447302,"name":"Eduardo U. M. Moreira","orcid":"0000-0002-9513-2342","position":1,"is_corresponding":false},{"id":447303,"name":"Camilla Valente Pires","orcid":"0000-0002-5470-1342","position":2,"is_corresponding":false},{"id":447304,"name":"Leticia M. Torres‐Martínez","orcid":"0000-0003-3328-0240","position":3,"is_corresponding":false},{"id":447305,"name":"Luiz F. F. Guimarães","orcid":"0000-0002-6346-027X","position":4,"is_corresponding":false},{"id":448312,"name":"Jéssica R. S. Alves","orcid":null,"position":5,"is_corresponding":false},{"id":448313,"name":"Bárbara A. S. Lima","orcid":null,"position":6,"is_corresponding":false},{"id":447306,"name":"Cor Jésus Fernandes Fontes","orcid":"0000-0003-2756-0588","position":7,"is_corresponding":false},{"id":448314,"name":"Helena L. Costa","orcid":null,"position":8,"is_corresponding":false},{"id":447307,"name":"Cristiana Ferreira Alves de Brito","orcid":"0000-0002-8888-5477","position":9,"is_corresponding":false},{"id":447308,"name":"Taís Nóbrega de Sousa","orcid":"0000-0002-6874-9427","position":10,"is_corresponding":false},{"id":447309,"name":"Francis B. Ntumngia","orcid":"0000-0001-9867-3534","position":11,"is_corresponding":false},{"id":398225,"name":"John H. Adams","orcid":"0000-0003-3707-7979","position":12,"is_corresponding":false},{"id":447310,"name":"Flora Satiko Kano","orcid":"0000-0002-2364-9772","position":13,"is_corresponding":false},{"id":447311,"name":"Luzia H. Carvalho","orcid":"0000-0001-5822-4187","position":14,"is_corresponding":false},{"id":448311,"name":"Camila Maia Pantuzzo Medeiros","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T22:00:56.736935Z","pmid":"32379804","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}