{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:47:03Z","timestamp":1782312423839,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n The blood\u2010stage merozoite surface protein 1 (\n Pv<\/jats:italic>\n MSP\n 19<\/jats:sub>\n ) of\n Plasmodium vivax<\/jats:italic>\n is a key target of naturally acquired antibodies. Effective humoral responses depend on T\u2010cell co\u2010stimulation, notably via the inducible co\u2010stimulator (ICOS) molecule. Polymorphisms in the\n ICOS<\/jats:italic>\n gene may influence antibody production, yet this relationship remains unexplored in naturally infected populations. We analysed 91 individuals with uncomplicated\n \n P. vivax<\/jats:italic>\n <\/jats:styled-content>\n infection in Venezuela. Total IgG antibodies against recombinant\n Pv<\/jats:italic>\n MSP\n 19<\/jats:sub>\n were measured by ELISA. A two\u2010step cluster analysis based on antibody reactivity indices (RI) was employed to categorize participants as low, medium, or high responders. Genotyping of\n ICOS<\/jats:italic>\n polymorphisms (rs4404254, rs4675379 and rs10183087) was performed using PCR\u2010based methods. Haplotype frequencies (inferred via the Expectation\u2013Maximization algorithm), linkage disequilibrium (LD) and associations under various genetic inheritance models were assessed using Haplo.stats (R environment) and SNPStats.\n Pv<\/jats:italic>\n MSP\n 19<\/jats:sub>\n \u2010specific IgG was detected in 70.3% of participants. The optimal three\u2010cluster solution (silhouette coefficient\u2009=\u20090.7) revealed significant differences in median RI across low (0.408), medium (0.862) and high responders (1.267;\n p<\/jats:italic>\n \u2009<\u20090.001).\n ICOS<\/jats:italic>\n genotypes and haplotypes showed no significant associations with antibody levels across any inheritance models, although strong LD was observed among the three loci (\n p<\/jats:italic>\n \u2009<\u20090.05). Notably, antibody responses positively correlated with the number of prior malarial episodes (\n r<\/jats:italic>\n \u2009=\u20090.803,\n p<\/jats:italic>\n \u2009<\u20090.0001). Our results indicate that the studied\n ICOS<\/jats:italic>\n polymorphisms do not significantly affect IgG responses against\n Pv<\/jats:italic>\n MSP\n 19<\/jats:sub>\n in this population, suggesting that variability in other costimulatory molecules may more strongly influence humoral immunity to\n \n P. vivax<\/jats:italic>\n <\/jats:styled-content>\n . These findings highlight the complexity of T\u2010cell\u2010mediated regulation of antibody responses and provide insights for optimizing vaccine strategies targeting blood\u2010stage malaria antigens.\n <\/jats:p>","DOI":"10.1111\/pim.70086","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:42:48Z","timestamp":1779964968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["No Evidence for Association Between\n ICOS<\/i>\n (a T\u2010Cell Co\u2010Stimulatory Molecule) Gene Polymorphisms and Anti\u2010\n MSP<\/scp>\n \u20101\n 19<\/sub>\n IgG<\/scp>\n Response in Venezuelan Endemic\n Plasmodium vivax<\/i>\n Malaria"],"prefix":"10.1111","volume":"48","author":[{"given":"Rublee D.","family":"Sevilla","sequence":"first","affiliation":[{"name":"Secci\u00f3n Inmunogen\u00e9tica, Laboratorio de Fisiopatolog\u00eda, Centro de Medicina Experimental \u201cMiguel Layrisse\u201d Instituto Venezolano de Investigaciones Cient\u00edficas Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0119-7776","authenticated-orcid":false,"given":"Oriana A.","family":"Regalado\u2010Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica y Vacunas Terap\u00e9uticas Ciudad Bol\u00edvar Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albina","family":"Wide","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda, Instituto de Medicina Tropical \u201cDr. F\u00e9lix Pifano\u201d Universidad Central de Venezuela Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-2429","authenticated-orcid":false,"given":"Rafael","family":"Puche\u2010Qui\u00f1onez","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Inmunogen\u00e9tica, Laboratorio de Fisiopatolog\u00eda, Centro de Medicina Experimental \u201cMiguel Layrisse\u201d Instituto Venezolano de Investigaciones Cient\u00edficas Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-2500","authenticated-orcid":false,"given":"Manuel A.","family":"Patarroyo","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n B\u00e1sica en Biolog\u00eda Molecular e Inmunolog\u00eda (GIBBMI) Fundaci\u00f3n Instituto de Inmunolog\u00eda de Colombia (FIDIC) Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Noya\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda, Instituto de Medicina Tropical \u201cDr. F\u00e9lix Pifano\u201d Universidad Central de Venezuela Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6227-5884","authenticated-orcid":false,"given":"Mercedes","family":"Fern\u00e1ndez\u2010Mestre","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Inmunogen\u00e9tica, Laboratorio de Fisiopatolog\u00eda, Centro de Medicina Experimental \u201cMiguel Layrisse\u201d Instituto Venezolano de Investigaciones Cient\u00edficas Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12816"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1350-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07324.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0834959100"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762007005000040"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149581"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-29"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35051100"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002510100351"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/89709"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008527"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","DOI":"10.1128\/iai.00468-21","article-title":"ICOS Expression Is Required for Maintenance but Not the Formation of Germinal Centers in the Spleen in Response to Plasmodium yoelii Infection","volume":"90","author":"O'Neal K. 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P.","year":"2013","journal-title":"GEN"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.08.010"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02926"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-022-04055-3"}],"container-title":["Parasite Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pim.70086","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pim.70086","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pim.70086","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:59:56Z","timestamp":1782309596000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pim.70086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/pim.70086"],"URL":"https:\/\/doi.org\/10.1111\/pim.70086","archive":["Portico"],"relation":{},"ISSN":["0141-9838","1365-3024"],"issn-type":[{"value":"0141-9838","type":"print"},{"value":"1365-3024","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"assertion":[{"value":"2026-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70086"}}