{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:54Z","timestamp":1788153534120,"version":"build-2803163510"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Long-term humoral immunity to\n                      <jats:italic>Plasmodium vivax<\/jats:italic>\n                      remains poorly understood, particularly the mechanisms sustaining persistent antibody responses to Duffy Binding Protein region II (DBPII), a key vaccine candidate. Here, a 15-year follow-up study of Amazonian malaria-exposed individuals investigated major cytokine pathways associated with sustained IgG responses to DBPII-related antigens, including DEKnull-2, an engineered immunogen targeting conserved DBPII epitopes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      As a proof-of-concept, this study was designed to compare two well-defined immunological phenotypes among\n                      <jats:italic>P. vivax-<\/jats:italic>\n                      exposed individuals: (i) Persistent Responders (PR, n = 11), who developed a long-lasting strain-transcending anti-DBPII immune response, defined here as sustained antibody responses to both DBPII and DEKnull-2, together with detectable binding-inhibitory antibody activity (BIAbs), throughout the follow-up period; and (ii) Non-Responders (NR; n = 14), who showed no detectable antibody response or BIAbs activity during follow-up. Cytokine responses were measured in supernatants of PBMC cultures stimulated with DBPII or DEKnull-2 by cytometric bead array (CBA), and IgG breadth was assessed using a panel of 16\u00a0P\n                      <jats:italic>. vivax<\/jats:italic>\n                      blood-stage antigens using Bio-Plex assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Regardless of the antigen used for stimulation,\n                      <jats:italic>P. vivax<\/jats:italic>\n                      -exposed individuals (NR and PR) exhibited lower IL-6 and TNF levels than malaria-na\u00efve non-exposed controls (NE, n = 14). Notably, the PR subgroup displayed a distinct profile characterized by a coordinated increase across inflammatory and anti-inflammatory cytokines. Even without antigen-specific stimulation, the PR group showed a distinct cytokine profile compared with NE controls, suggesting that host-intrinsic factors may influence DBPII-specific immune responses. Finally, PR (but not NR) displayed broader long-lasting antibody responses to multiple\n                      <jats:italic>P. vivax<\/jats:italic>\n                      blood-stage antigens, even in the absence of frequent reinfection-induced boosting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Overall, these findings suggest that the PR profile is associated with a distinct and balanced cytokine profile. Our hypothesis-generating findings may improve our understanding of immune responses to\n                      <jats:italic>P. vivax<\/jats:italic>\n                      blood-stage antigens and inform future vaccine development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1899417","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:29:31Z","timestamp":1788150571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytokine signatures associated with persistent antibody responses to multiple Plasmodium vivax blood-stage antigens"],"prefix":"10.3389","volume":"17","author":[{"given":"S\u00e2mick L.","family":"Moreira-Nascimento","sequence":"first","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Fernanda A.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela M.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia L.","family":"Afonso","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor H. G.","family":"Gunderman","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara A.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie C. P.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Le\u00f4nidas e Maria Deane, Fiocruz Amaz\u00f4nia","place":["Manaus, Amazonas, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Le\u00f4nidas e Maria Deane, Fiocruz Amaz\u00f4nia","place":["Manaus, Amazonas, Brazil"]},{"name":"Universidade Federal do Amazonas","place":["Manaus, Amazonas, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus V. G.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Le\u00f4nidas e Maria Deane, Fiocruz Amaz\u00f4nia","place":["Manaus, Amazonas, Brazil"]},{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg\u00f3rio G.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]},{"name":"Universidade Federal de Minas Gerais, Centro de Tecnologia de Vacinas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea J.","family":"Longley","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research","place":["Parkville, Victoria, Australia"]},{"name":"Department of Medical Biology, The University of Melbourne","place":["Melbourne, VIC, Australia"]},{"name":"Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Mueller","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research","place":["Parkville, Victoria, Australia"]},{"name":"Department of Medical Biology, The University of Melbourne","place":["Melbourne, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lis R. D. V.","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis B.","family":"Ntumngia","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Adams","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a","family":"Teixeira-Carvalho","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luzia H.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora S.","family":"Kano","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Fiocruz, Instituto Ren\u00e9 Rachou, Fiocruz Minas","place":["Belo Horizonte, Minas Gerais, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(09)70177-x","article-title":"Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite","volume":"9","author":"Mueller","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1080\/14760584.2021.1880898","article-title":"Progress towards the development of a P. vivax vaccine","volume":"20","author":"De","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e28673","DOI":"10.7554\/eLife.28673","article-title":"Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development","volume":"6","author":"Franca","year":"2017","journal-title":"Elife"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.910236","article-title":"Plasmodium vivax vaccine: What is the best way to go","volume":"13","author":"da Veiga","year":"2022","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf1782","article-title":"Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection","volume":"15","author":"Hou","year":"2023","journal-title":"Sci Transl Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-12-407826-0.00001-1","article-title":"In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax","volume":"169","author":"Barnwell","year":"1989","journal-title":"J Exp Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90295-p","article-title":"The Duffy receptor family of Plasmodium knowlesi is located within the micronemes of invasive malaria merozoites","volume":"63","author":"Adams","year":"1990","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197608052950602","article-title":"The resistance factor to Plasmodium vivax in blacks. 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