{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T05:09:03Z","timestamp":1778389743779,"version":"3.51.4"},"reference-count":122,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"crossref","award":["VPPCB-007-FIO-18-2-46"],"award-info":[{"award-number":["VPPCB-007-FIO-18-2-46"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["425.422\/2016-0"],"award-info":[{"award-number":["425.422\/2016-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)\u2014Programa de Apoio a N\u00facleos de Excel\u00eancia","award":["E-26\/010.001268\/2016"],"award-info":[{"award-number":["E-26\/010.001268\/2016"]}]},{"DOI":"10.13039\/501100004586","name":"Apoio a Grupos Emergentes de Pesquisa","doi-asserted-by":"publisher","award":["E26\/211.112\/2019"],"award-info":[{"award-number":["E26\/211.112\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brazil (CAPES)\u2014Finance Code 001"},{"DOI":"10.13039\/501100018824","name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Neuroimunomodula\u00e7\u00e3o","doi-asserted-by":"crossref","award":["465489\/2014-1"],"award-info":[{"award-number":["465489\/2014-1"]}],"id":[{"id":"10.13039\/501100018824","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Rede de Neuroinflama\u00e7\u00e3o","award":["26010.002418\/2019"],"award-info":[{"award-number":["26010.002418\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual stage Pfs48\/45-6c protein genetically fused to GMZ2, which is an asexual stage vaccine construct consisting of conserved domains of Glutamate-Rich Protein (GLURP) and Merozoite Surface Protein-3 (MSP-3). Previous studies showed that GMZ2.6c is widely recognized by antibodies from individuals living in endemic areas of Brazil and that levels of anti-GMZ2.6c increase with malaria exposure and may contribute to immunity against the parasite. As cell-mediated responses are crucial for parasite control and protection, identifying antigens that elicit antigen-specific T cell recall in naturally exposed populations is the key to vaccine development. This study aimed to evaluate the cellular immune response against GMZ2.6c and its components (MSP-3, GLURP, and Pfs48\/45) and to identify promiscuous T cell epitopes in individuals exposed to malaria in the Brazilian Amazon, considering the impact of active P. falciparum infection on antigen-specific T cell recall. Methods: This study was carried out using peripheral blood mononuclear cells (PBMCs) from individuals with active P. falciparum infection (PFI) and non-infected individuals exposed to malaria (NI) from Cruzeiro do Sul and M\u00e2ncio Lima, Acre State, and Guajar\u00e1, Amazonas State. The PBMCs were stimulated with GMZ2.6c and its components, and cellular activation, CD4+ and CD8+ memory T cell subsets, and cytokine production were evaluated by flow cytometry. IFN-\u03b3-secreting T cells were quantified by ELISpot using predicted T cell epitopes. Results: The individuals infected by P. falciparum displayed more CD8+ T cell activation in response to MSP-3 and Pfs48\/45 and an increase in CD4+ TCM cells and a reduction in CD4+ TEM cells following stimulation with Pfs48\/45 and GMZ2.6c. The PBMCs from both groups showed elevated production of IL-6 and TNF after stimulation with GMZ2.6c, MSP-3, and Pfs48\/45, but only the non-infected individuals had high levels of IL-10. T cell epitope prediction identified sequences within MSP-3, GLURP, and Pfs48\/45 that elicited IFN-\u03b3 responses in both the non-infected and P. falciparum-infected individuals. Conclusions: Individuals exhibit cellular immune responses to MSP-3 and Pfs48\/45 that are recalled following GMZ2.6c stimulation. P. falciparum infection may modulate immune response, inducing a prominent pro-inflammatory response. Conversely, in the absence of the parasite, the individuals displayed balanced Th1\/Th2 cytokine production. Several promiscuous T cell epitopes were able to recall IFN-\u03b3 responses. Further studies are needed to fully ascertain the potential of GMZ2.6c as a protective candidate vaccine against malaria.<\/jats:p>","DOI":"10.3390\/vaccines14050423","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:10:52Z","timestamp":1778267452000},"page":"423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular Immune Response and T Cell Epitope Mapping of Plasmodium falciparum Chimeric Vaccine Candidate GMZ2.6c and Its Components (MSP-3, GLURP and Pfs48\/45) in Individuals Naturally Exposed to Malaria in Brazilian Amazon"],"prefix":"10.3390","volume":"14","author":[{"given":"Barbara de Oliveira","family":"Baptista","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabela Ferreira","family":"Soares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunoparasitologia, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-2898","authenticated-orcid":false,"given":"Hugo Amorim dos Santos","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenifer Peixoto de","family":"Barros","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-2605","authenticated-orcid":false,"given":"Evelyn Kety Pratt","family":"Riccio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7775-6901","authenticated-orcid":false,"given":"Rodrigo Medeiros","family":"Martorano","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Doen\u00e7as Infecciosas na Amaz\u00f4nia Ocidental, Universidade Federal do Acre\u2013Campus Floresta (UFAC), Cruzeiro do Sul 69895-000, AC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9772-849X","authenticated-orcid":false,"given":"Rodrigo Nunes","family":"Rodrigues-da-Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hantaviroses e Rickettsioses, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda Eva","family":"Amoah","sequence":"additional","affiliation":[{"name":"Immunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra P.O. Box LG 25, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1489-8742","authenticated-orcid":false,"given":"Susheel Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine and Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"},{"name":"Statens Serum Institut (SSI), DK-2300 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Theisen","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine and Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"},{"name":"Statens Serum Institut (SSI), DK-2300 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5848-404X","authenticated-orcid":false,"given":"Josu\u00e9 da Costa","family":"Lima-Junior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunoparasitologia, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo Renato Rivas","family":"Totino","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9075-1470","authenticated-orcid":false,"given":"Cl\u00e1udio Tadeu","family":"Daniel-Ribeiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-5889","authenticated-orcid":false,"given":"Lilian Rose","family":"Pratt-Riccio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Mal\u00e1ria, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Centro de Pesquisa, Diagn\u00f3stico e Treinamento em Mal\u00e1ria (CPD-Mal), Funda\u00e7\u00e3o Oswaldo Cruz e Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, February 16). World Malaria Report 2024. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/infdis\/jiy637","article-title":"Comparative Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Malaria in Ugandan Children","volume":"219","author":"Yeka","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/cid\/ciaa628","article-title":"Clinical and In Vitro Resistance of Plasmodium falciparum to Artesunate-Amodiaquine in Cambodia","volume":"73","author":"Leang","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.01949-20","article-title":"Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019","volume":"65","author":"Dimbu","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1186\/s12936-021-04021-5","article-title":"Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria and Prevalence of Molecular Markers Associated with Artemisinin and Partner Drug Resistance in Uganda","volume":"20","author":"Ebong","year":"2021","journal-title":"Malar. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12936-021-03585-6","article-title":"Anti-Malarial Efficacy and Resistance Monitoring of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine Shows Inadequate Efficacy in Children in Burkina Faso, 2017\u20132018","volume":"20","author":"Moriarty","year":"2021","journal-title":"Malar. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/infdis\/jiab352","article-title":"High Prevalence of Plasmodium falciparum K13 Mutations in Rwanda Is Associated With Slow Parasite Clearance After Treatment With Artemether-Lumefantrine","volume":"225","author":"Straimer","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00207-22","DOI":"10.1128\/aac.00207-22","article-title":"Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria among Children in Western Kenya, 2016 to 2017","volume":"66","author":"Westercamp","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/s41564-023-01461-4","article-title":"Plasmodium falciparum Resistant to Artemisinin and Diagnostics Have Emerged in Ethiopia","volume":"8","author":"Fola","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hancock, P.A., Hendriks, C.J.M., Tangena, J.A., Gibson, H., Hemingway, J., Coleman, M., Gething, P.W., Cameron, E., Bhatt, S., and Moyes, C.L. (2020). Mapping Trends in Insecticide Resistance Phenotypes in African Malaria Vectors. PLoS Biol., 18.","DOI":"10.1101\/2020.01.06.895656"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Golassa, L., Messele, A., Amambua-Ngwa, A., and Swedberg, G. (2020). High Prevalence and Extended Deletions in Plasmodium falciparum Hrp2\/3 Genomic Loci in Ethiopia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241807"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1080\/22221751.2020.1815590","article-title":"Misdiagnosis of Imported falciparum Malaria from African Areas Due to an Increased Prevalence of Pfhrp2\/Pfhrp3 Gene Deletion: The Djibouti Case","volume":"9","author":"Iriart","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12936-021-03629-x","article-title":"Detection of High Prevalence of Plasmodium falciparum Histidine-Rich Protein 2\/3 Gene Deletions in Assosa Zone, Ethiopia: Implication for Malaria Diagnosis","volume":"20","author":"Alemayehu","year":"2021","journal-title":"Malar. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41564-021-00962-4","article-title":"Plasmodium falciparum Is Evolving to Escape Malaria Rapid Diagnostic Tests in Ethiopia","volume":"6","author":"Feleke","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1186\/s13071-021-05026-4","article-title":"Emergence of the Invasive Malaria Vector Anopheles stephensi in Khartoum State, Central Sudan","volume":"14","author":"Ahmed","year":"2021","journal-title":"Parasit. Vectors"},{"key":"ref_16","unstructured":"World Health Organization (2023, October 19). WHO Recommends Groundbreaking Malaria Vaccine for Children at Risk. Available online: https:\/\/www.who.int\/news\/item\/06-10-2021."},{"key":"ref_17","unstructured":"World Health Organization (2024, February 14). World Malaria Report 2023. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2023."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/s12936-021-03961-2","article-title":"Seven-Year Kinetics of RTS,S\/AS01-Induced Anti-CSP Antibodies in Young Kenyan Children","volume":"20","author":"Mugo","year":"2021","journal-title":"Malar. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0140-6736(23)02511-4","article-title":"Safety and Efficacy of Malaria Vaccine Candidate R21\/Matrix-M in African Children: A Multicentre, Double-Blind, Randomised, Phase 3 Trial","volume":"403","author":"Datoo","year":"2024","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1016\/j.vaccine.2016.03.016","article-title":"Synthetic TLR4 Agonists Enhance Functional Antibodies and CD4+ T-Cell Responses against the Plasmodium falciparum GMZ2.6C Multi-Stage Vaccine Antigen","volume":"34","author":"Baldwin","year":"2016","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12936-021-04020-6","article-title":"Naturally Acquired Antibody Response to a Plasmodium falciparum Chimeric Vaccine Candidate GMZ2.6c and Its Components (MSP-3, GLURP, and Pfs48\/45) in Individuals Living in Brazilian Malaria-Endemic Areas","volume":"21","author":"Baptista","year":"2022","journal-title":"Malar. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Baptista Bde, O., Souza, A.B.L.d.e., Oliveira, L.S.d.e., Souza HAdos, S.d.e., Barros, J.P.d.e., Queiroz, L.T.d.e., Souza, R.M.d.e., Amoah, L.E., Singh, S.K., and Theisen, M. (2023). B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon. Vaccines, 11.","DOI":"10.3390\/vaccines11020446"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.vaccine.2018.03.023","article-title":"T-Cell Responses against Malaria: Effect of Parasite Antigen Diversity and Relevance for Vaccine Development","volume":"36","author":"Nlinwe","year":"2018","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6529681","DOI":"10.1155\/2018\/6529681","article-title":"Immune Response and Evasion Mechanisms of Plasmodium falciparum Parasites","volume":"2018","author":"Belachew","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.4049\/jimmunol.165.3.1453","article-title":"The Complexity of Protective Immunity Against Liver-Stage Malaria","volume":"165","author":"Doolan","year":"2000","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12628","DOI":"10.1111\/pim.12628","article-title":"Immune Effector Mechanisms in Malaria: An Update Focusing on Human Immunity","volume":"41","author":"Moormann","year":"2019","journal-title":"Parasite Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mandala, W.L., Harawa, V., Dzinjalamala, F., and Tembo, D. (2021). The Role of Different Components of the Immune System against Plasmodium falciparum Malaria: Possible Contribution towards Malaria Vaccine Development. Mol. Biochem. Parasitol., 246.","DOI":"10.1016\/j.molbiopara.2021.111425"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1182\/blood-2009-06-227546","article-title":"Memories That Last Forever: Strategies for Optimizing Vaccine T-Cell Memory","volume":"115","author":"Ahlers","year":"2010","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1086\/432519","article-title":"How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria","volume":"77","author":"Kwiatkowski","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lima-Junior, J.D., and Pratt-Riccio, L.R. (2016). Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax Infection. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00013"},{"key":"ref_31","unstructured":"(2023, December 12). Ministry of Health Malaria Epidemiological Surveillance Information System, Available online: http:\/\/www.saude.gov.br\/sivep_malaria."},{"key":"ref_32","first-page":"263","article-title":"Detection and Identification of the Four Malaria Parasite Species Infecting Humans by PCR Amplification","volume":"50","author":"Snounou","year":"1996","journal-title":"Methods Mol. Biol."},{"key":"ref_33","unstructured":"(2020, November 19). Ministry of Health Guide to Malaria Treatment in Brazil, Available online: http:\/\/bvsms.saude.gov.br\/bvs\/publicacoes\/guia_tratamento_malaria_brasil.pdf."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fleri, W., Paul, S., Dhanda, S.K., Mahajan, S., Xu, X., Peters, B., and Sette, A. (2017). The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00278"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1110\/ps.0239403","article-title":"Reliable Prediction of T-Cell Epitopes Using Neural Networks with Novel Sequence Representations","volume":"12","author":"Nielsen","year":"2003","journal-title":"Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Peters, B., and Sette, A. (2005). Generating Quantitative Models Describing the Sequence Specificity of Biological Processes with the Stabilized Matrix Method. BMC Bioinform., 6.","DOI":"10.1186\/1471-2105-6-132"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1745-7580-4-2","article-title":"Quantitative Peptide Binding Motifs for 19 Human and Mouse MHC Class i Molecules Derived Using Positional Scanning Combinatorial Peptide Libraries","volume":"4","author":"Sidney","year":"2008","journal-title":"Immunome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s12936-017-1955-0","article-title":"Antibody Responses to Two New Lactococcus lactis-Produced Recombinant Pfs48\/45 and Pfs230 Proteins Increase with Age in Malaria Patients Living in the Central Region of Ghana","volume":"16","author":"Acquah","year":"2017","journal-title":"Malar. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12934-018-0902-2","article-title":"Lactococcus lactis Provides an Efficient Platform for Production of Disulfide-Rich Recombinant Proteins from Plasmodium falciparum","volume":"17","author":"Singh","year":"2018","journal-title":"Microb. Cell Fact."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1365-3024.2007.00948.x","article-title":"A Longitudinal Study of Immune Responses to Plasmodium falciparum Sexual Stage Antigens in Tanzanian Adults","volume":"29","author":"Bousema","year":"2007","journal-title":"Parasite Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17148","DOI":"10.1074\/jbc.M700948200","article-title":"Epitope Analysis of the Malaria Surface Antigen Pfs48\/45 Identifies a Subdomain That Elicits Transmission Blocking Antibodies","volume":"282","author":"Outchkourov","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6862","DOI":"10.1016\/j.vaccine.2009.09.011","article-title":"Safety and Immunogenicity of GMZ2\u2014A MSP3\u2013GLURP Fusion Protein Malaria Vaccine Candidate","volume":"27","author":"Esen","year":"2009","journal-title":"Vaccine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6698","DOI":"10.1016\/j.vaccine.2010.07.085","article-title":"Safety and Immunogenicity of the Malaria Vaccine Candidate GMZ2 in Malaria-Exposed, Adult Individuals from Lambar\u00e9n\u00e9, Gabon","volume":"28","author":"Szywon","year":"2010","journal-title":"Vaccine"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"B\u00e9lard, S., Issifou, S., Hounkpatin, A.B., Schaumburg, F., Ngoa, U.A., Esen, M., Fendel, R., de Salazar, P.M., M\u00fcrbeth, R.E., and Milligan, P. (2011). A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022525"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1128\/IAI.05288-11","article-title":"Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48\/45 and Pfs230 in an Area of Seasonal Transmission","volume":"79","author":"Roeffen","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/infdis\/jit185","article-title":"The Malaria Vaccine Candidate GMZ2 Elicits Functional Antibodies in Individuals From Malaria Endemic and Non-Endemic Areas","volume":"208","author":"Jepsen","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1475-2875-12-51","article-title":"Humoral Immune Response to Plasmodium falciparum Vaccine Candidate GMZ2 and Its Components in Populations Naturally Exposed to Seasonal Malaria in Ethiopia","volume":"12","author":"Mamo","year":"2013","journal-title":"Malar. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1016\/j.vaccine.2016.07.041","article-title":"A Phase 2b Randomized, Controlled Trial of the Efficacy of the GMZ2 Malaria Vaccine in African Children","volume":"34","author":"Sirima","year":"2016","journal-title":"Vaccine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1093\/cid\/ciy1087","article-title":"Controlled Human Malaria Infection of Healthy Adults With Lifelong Malaria Exposure to Assess Safety, Immunogenicity, and Efficacy of the Asexual Blood Stage Malaria Vaccine Candidate GMZ2","volume":"69","author":"Lalremruata","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s12936-022-04169-8","article-title":"Cellular and Antibody Response in GMZ2-Vaccinated Gabonese Volunteers in a Controlled Human Malaria Infection Trial","volume":"21","author":"Nouatin","year":"2022","journal-title":"Malar. J."},{"key":"ref_51","first-page":"646","article-title":"The Role of T Cells in Pathogenesis and Protective Immunity to Murine Malaria","volume":"75","author":"Waki","year":"1992","journal-title":"Immunology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/S0140-6736(02)09784-2","article-title":"Immunity to Malaria after Administration of Ultra-Low Doses of Red Cells Infected with Plasmodium falciparum","volume":"360","author":"Pombo","year":"2002","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/eji.200939525","article-title":"Involvement of CD8+ T Cells in Protective Immunity against Murine Blood-Stage Infection with Plasmodium yoelii 17XL Strain","volume":"40","author":"Imai","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e04232","DOI":"10.7554\/eLife.04232","article-title":"Cytotoxic Activities of CD8+ T Cells Collaborate with Macrophages to Protect against Blood-Stage Murine Malaria","volume":"4","author":"Imai","year":"2015","journal-title":"eLife"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.1128\/iai.65.10.4090-4093.1997","article-title":"Rapid Reemergence of T Cells into Peripheral Circulation Following Treatment of Severe and Uncomplicated Plasmodium falciparum Malaria","volume":"65","author":"Hviid","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1046\/j.1365-3024.2000.00307.x","article-title":"Apoptosis Modulation in Mononuclear Cells Recovered from Individuals Exposed to Plasmodium falciparum Infection","volume":"22","author":"Balde","year":"2000","journal-title":"Parasite Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1128\/CVI.13.3.376-379.2006","article-title":"Characterization of Peripheral Blood Lymphocyte Subsets in Patients with Acute Plasmodium falciparum and P. vivax Malaria Infections at Wonji Sugar Estate, Ethiopia","volume":"13","author":"Kassa","year":"2006","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1186\/1475-2875-12-455","article-title":"Analysis of Lymphocytes in Patients with Plasmodium vivax Malaria and Its Relation to the Annexin-A1 and IL-10","volume":"12","author":"Borges","year":"2013","journal-title":"Malar. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.4269\/ajtmh.18-0835","article-title":"Safety and Differential Antibody and T-Cell Responses to the Plasmodium falciparum Sporozoite Malaria Vaccine, PfSPZ Vaccine, by Age in Tanzanian Adults, Adolescents, Children, and Infants","volume":"100","author":"Jongo","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Millington, O.R., Di Lorenzo, C., Phillips, R.S., Garside, P., and Brewer, J.M. (2006). Suppression of Adaptive Immunity to Heterologous Antigens during Plasmodium Infection through Hemozoin-Induced Failure of Dendritic Cell Function. J. Biol., 5.","DOI":"10.1186\/jbiol34"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S1074-7613(00)80513-0","article-title":"Degenerate Cytotoxic T Cell Epitopes from P. falciparum Restricted by Multiple HLA-A and HLA-B Supertype Alleles","volume":"7","author":"Doolan","year":"1997","journal-title":"Immunity"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kusi, K.A., Aggor, F.E., Amoah, L.E., Anum, D., Nartey, Y., Amoako-Sakyi, D., Obiri-Yeboah, D., Hollingdale, M., Ganeshan, H., and Belmonte, M. (2020). Identification of Plasmodium falciparum Circumsporozoite Protein-Specific CD8+ T Cell Epitopes in a Malaria Exposed Population. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228177"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6961","DOI":"10.4049\/jimmunol.171.12.6961","article-title":"Protective Immunity Induced with Malaria Vaccine, RTS,S, Is Linked to Plasmodium falciparum Circumsporozoite Protein-Specific CD4+ and CD8+ T Cells Producing IFN-\u03b3","volume":"171","author":"Sun","year":"2003","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1038\/ncomms3836","article-title":"Protective CD8+ T-Cell Immunity to Human Malaria Induced by Chimpanzee Adenovirus-MVA Immunisation","volume":"4","author":"Ewer","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14509","DOI":"10.1073\/pnas.0806727105","article-title":"Blood-Stage Plasmodium Infection Induces CD8+ T Lymphocytes to Parasite-Expressed Antigens, Largely Regulated by CD8\u03b1+ Dendritic Cells","volume":"105","author":"Lundie","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1365-2567.2010.03363.x","article-title":"Phenotypic and Functional Profiling of Malaria-Induced CD8 and CD4 T Cells during Blood-Stage Infection with Plasmodium yoelii","volume":"132","author":"Chandele","year":"2011","journal-title":"Immunology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/infdis\/jir656","article-title":"Blood-Stage Plasmodium berghei Infection Generates a Potent, Specific CD8+ T-Cell Response Despite Residence Largely in Cells Lacking MHC I Processing Machinery","volume":"204","author":"Lau","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.4049\/jimmunol.1003955","article-title":"Granzyme B Expression by CD8+ T Cells Is Required for the Development of Experimental Cerebral Malaria","volume":"186","author":"Haque","year":"2011","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1002\/eji.201141539","article-title":"Type I Interferons Suppress CD4+ T-Cell-Dependent Parasite Control during Blood-Stage Plasmodium Infection","volume":"41","author":"Haque","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.celrep.2013.11.002","article-title":"PD-1 Dependent Exhaustion of CD8+ T Cells Drives Chronic Malaria","volume":"5","author":"Faleiro","year":"2013","journal-title":"Cell Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Horne-Debets, J.M., Karunarathne, D.S., Faleiro, R.J., Poh, C.M., Renia, L., and Wykes, M.N. (2016). Mice Lacking Programmed Cell Death-1 Show a Role for CD8+ T Cells in Long-Term Immunity against Blood-Stage Malaria. Sci. Rep., 6.","DOI":"10.1038\/srep26210"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Teirlinck, A.C., McCall, M.B.B., Roestenberg, M., Scholzen, A., Woestenenk, R., de Mast, Q., van der Ven, A.J.A.M., Hermsen, C.C., Luty, A.J.F., and Sauerwein, R.W. (2011). Longevity and Composition of Cellular Immune Responses Following Experimental Plasmodium falciparum Malaria Infection in Humans. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002389"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/intimm\/2.12.1121","article-title":"In Vitro Cell-Mediated Immune Responses to Plasmodium falciparum Schizont Antigens in Adults from a Malaria Endemic Area: CD8+ T Lymphocytes Inhibit the Response of Low Responder Individuals","volume":"2","author":"Mshana","year":"1990","journal-title":"Int. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/eji.200324514","article-title":"Disulfide Bonds in Merozoite Surface Protein 1 of the Malaria Parasite Impede Efficient Antigen Processing and Affect the in vivo Antibody Response","volume":"34","author":"Hensmann","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1074-7613(00)80191-0","article-title":"Control of Antigen Presentation by a Single Protease Cleavage Site","volume":"12","author":"Antoniou","year":"2000","journal-title":"Immunity"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.4049\/jimmunol.175.4.2252","article-title":"Insertion of the Dibasic Motif in the Flanking Region of a Cryptic Self-Determinant Leads to Activation of the Epitope-Specific T Cells","volume":"175","author":"Zhu","year":"2005","journal-title":"J. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/imr.12835","article-title":"Using Two Phases of the CD4 T Cell Response to Blood-Stage Murine Malaria to Understand Regulation of Systemic Immunity and Placental Pathology in Plasmodium falciparum Infection","volume":"293","author":"Gbedande","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Stephens, R., and Langhorne, J. (2010). Effector Memory Th1 CD4 T Cells Are Maintained in a Mouse Model of Chronic Malaria. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001208"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Opata, M.M., Ibitokou, S.A., Carpio, V.H., Marshall, K.M., Dillon, B.E., Carl, J.C., Wilson, K.D., Arcari, C.M., and Stephens, R. (2018). Protection by and Maintenance of CD4 Effector Memory and Effector T Cell Subsets in Persistent Malaria Infection. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006960"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e00744-16","DOI":"10.1128\/IAI.00744-16","article-title":"Chronic Plasmodium chabaudi Infection Generates CD4 Memory T Cells with Increased T Cell Receptor Sensitivity but Poor Secondary Expansion and Increased Apoptosis","volume":"85","author":"Opata","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/infdis\/jiw147","article-title":"Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10","volume":"214","author":"Jagannathan","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.4049\/jimmunol.1202438","article-title":"Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion","volume":"190","author":"Illingworth","year":"2013","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Hojo-Souza, N.S., Pereira, D.B., Passos, L.S.A., Gazzinelli-Guimar\u00e3es, P.H., Cardoso, M.S., Tada, M.S., Zanini, G.M., Bartholomeu, D.C., Fujiwara, R.T., and Bueno, L.L. (2015). Phenotypic Profiling of CD8+ T Cells during Plasmodium vivax Blood-Stage Infection. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-0762-x"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Chelimo, K., Embury, P.B., Odada Sumba, P., Vulule, J., Ofulla, A.V., Long, C., Kazura, J.W., and Moormann, A.M. (2011). Age-Related Differences in Naturally Acquired T Cell Memory to Plasmodium falciparum Merozoite Surface Protein 1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024852"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1086\/339408","article-title":"Absolute Levels and Ratios of Pro-inflammatory and Anti-Inflammatory Cytokine Production in vitro Predict Clinical Immunity to Plasmodium falciparum Malaria","volume":"185","author":"Dodoo","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1186\/s12936-017-2148-6","article-title":"Both Inflammatory and Regulatory Cytokine Responses to Malaria Are Blunted with Increasing Age in Highly Exposed Children","volume":"16","author":"Farrington","year":"2017","journal-title":"Malar. J."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Frimpong, A., Amponsah, J., Adjokatseh, A.S., Agyemang, D., Bentum-Ennin, L., Ofori, E.A., Kyei-Baafour, E., Akyea-Mensah, K., Adu, B., and Mensah, G.I. (2020). Asymptomatic Malaria Infection Is Maintained by a Balanced Pro- and Anti-Inflammatory Response. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.559255"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7785180","DOI":"10.1155\/2021\/7785180","article-title":"Recent Advances in Understanding the Inflammatory Response in Malaria: A Review of the Dual Role of Cytokines","volume":"2021","author":"Popa","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.bbagen.2016.04.003","article-title":"Tumor Necrosis Factor Reduces Plasmodium falciparum Growth and Activates Calcium Signaling in Human Malaria Parasites","volume":"1860","author":"Cruz","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"He, X., Xia, L., Tumas, K.C., Wu, J., and Su, X.Z. (2020). Type I Interferons and Malaria: A Double-Edge Sword Against a Complex Parasitic Disease. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.594621"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12455","DOI":"10.1111\/pim.12455","article-title":"IL-6 Promotes CD4+ T-Cell and B-Cell Activation during Plasmodium Infection","volume":"39","author":"Sebina","year":"2017","journal-title":"Parasite Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Perez-Mazliah, D., and Langhorne, J. (2015). CD4 T-Cell Subsets in Malaria: TH1\/TH2 Revisited. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00671"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1128\/IAI.67.7.3424-3429.1999","article-title":"Interleukin-10 Responses to Liver-Stage Antigen 1 Predict Human Resistance to Plasmodium falciparum","volume":"67","author":"Kurtis","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12936-015-0681-8","article-title":"Naturally-Acquired Cellular Immune Response against Plasmodium vivax Merozoite Surface Protein-1 Paralog Antigen","volume":"14","author":"Changrob","year":"2015","journal-title":"Malar. J."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Portugal, S., Moebius, J., Skinner, J., Doumbo, S., Doumtabe, D., Kone, Y., Dia, S., Kanakabandi, K., Sturdevant, D.E., and Virtaneva, K. (2014). Exposure-Dependent Control of Malaria-Induced Inflammation in Children. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004079"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Boyle, M.J., Jagannathan, P., Bowen, K., McIntyre, T.I., Vance, H.M., Farrington, L.A., Schwartz, A., Nankya, F., Naluwu, K., and Wamala, S. (2017). The Development of Plasmodium falciparum-Specific IL10 CD4 T Cells and Protection from Malaria in Children in an Area of High Malaria Transmission. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01329"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/ni.2180","article-title":"Therapeutic Blockade of PD-L1 and LAG-3 Rapidly Clears Established Blood-Stage Plasmodium Infection","volume":"13","author":"Butler","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Hafalla, J.C.R., Claser, C., Couper, K.N., Grau, G.E., Renia, L., de Souza, J.B., and Riley, E.M. (2012). The CTLA-4 and PD-1\/PD-L1 Inhibitory Pathways Independently Regulate Host Resistance to Plasmodium-Induced Acute Immune Pathology. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002504"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.micinf.2016.06.003","article-title":"Surface Expression of Inhibitory (CTLA-4) and Stimulatory (OX40) Receptors by CD4+ Regulatory T Cell Subsets Circulating in Human Malaria","volume":"18","author":"Lima","year":"2016","journal-title":"Microbes Infect."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Mackroth, M.S., Abel, A., Steeg, C., Schulze zur Wiesch, J., and Jacobs, T. (2016). Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005909"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Abel, A., Steeg, C., Aminkiah, F., Addai-Mensah, O., Addo, M., Gagliani, N., Casar, C., Yar, D.D., Owusu-Dabo, E., and Jacobs, T. (2018). Differential Expression Pattern of Co-Inhibitory Molecules on CD4+ T Cells in Uncomplicated versus Complicated Malaria. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22659-1"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Calle, C.L., Fendel, R., Singh, A., Richie, T.L., Hoffman, S.L., Kremsner, P.G., and Mordm\u00fcller, B. (2021). Expansion of Functional Myeloid-Derived Suppressor Cells in Controlled Human Malaria Infection. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.625712"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/nm.4395","article-title":"Regulatory T cells impede acute and long-term immunity to blood-stage malaria through CTLA-4","volume":"23","author":"Kurup","year":"2017","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12936-016-1098-8","article-title":"Measurement of ex vivo ELISpot Interferon-Gamma Recall Responses to Plasmodium falciparum AMA1 and CSP in Ghanaian Adults with Natural Exposure to Malaria","volume":"15","author":"Ganeshan","year":"2016","journal-title":"Malar. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.4049\/jimmunol.169.6.2956","article-title":"Innate Immune Response to Malaria: Rapid Induction of IFN-\u03b3 from Human NK Cells by Live Plasmodium falciparum-Infected Erythrocytes","volume":"169","author":"Riley","year":"2002","journal-title":"J. Immunol."},{"key":"ref_106","first-page":"348","article-title":"Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria","volume":"9","author":"Torre","year":"2002","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1128\/CVI.00009-14","article-title":"Submicroscopic Infections with Plasmodium falciparum during Pregnancy and Their Association with Circulating Cytokine, Chemokine, and Cellular Profiles","volume":"21","author":"Ibitokou","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1189\/jlb.0310137","article-title":"Interferon-\u03b3\u2014Central Mediator of Protective Immune Responses against the Pre-Erythrocytic and Blood Stage of Malaria","volume":"88","author":"McCall","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"King, T., and Lamb, T. (2015). Interferon-\u03b3: The Jekyll and Hyde of Malaria. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005118"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"590","DOI":"10.4269\/ajtmh.2003.68.590","article-title":"Association of Interferon-Gamma Responses to Pre-Erythrocytic Stage Vaccine Candidate Antigens of Plasmodium falciparum in Young Kenyan Children with Improved Hemoglobin Levels: XV. Asembo Bay Cohort Project","volume":"68","author":"Lal","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5135","DOI":"10.1128\/IAI.72.9.5135-5142.2004","article-title":"Gamma Interferon Responses to Plasmodium falciparum Liver-Stage Antigen 1 and Thrombospondin-Related Adhesive Protein and Their Relationship to Age, Transmission Intensity, and Protection against Malaria","volume":"72","author":"John","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nm1009","article-title":"A CD4+ T-Cell Immune Response to a Conserved Epitope in the Circumsporozoite Protein Correlates with Protection from Natural Plasmodium falciparum Infection and Disease","volume":"10","author":"Reece","year":"2004","journal-title":"Nat. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Todryk, S.M., Bejon, P., Mwangi, T., Plebanski, M., Urban, B., Marsh, K., Hill, A.V.S., and Flanagan, K.L. (2008). Correlation of Memory T Cell Responses against TRAP with Protection from Clinical Malaria, and CD4+ CD25high T Cells with Susceptibility in Kenyans. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002027"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1365-3024.2009.01130.x","article-title":"Humoral and Cell-Mediated Immunity to MSP3 Peptides in Adults Immunized with MSP3 in Malaria Endemic Area, Burkina Faso","volume":"31","author":"Nebie","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.vaccine.2009.01.097","article-title":"Cell-Mediated Immunity Elicited by the Blood Stage Malaria Vaccine Apical Membrane Antigen 1 in Malian Adults: Results of a Phase I Randomized Trial","volume":"27","author":"Lyke","year":"2009","journal-title":"Vaccine"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1017\/S0031182015001341","article-title":"Naturally Acquired Immunity to Sexual Stage P. falciparum Parasites","volume":"143","author":"Stone","year":"2016","journal-title":"Parasitology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/s41467-017-02646-2","article-title":"Unravelling the Immune Signature of Plasmodium falciparum Transmission-Reducing Immunity","volume":"9","author":"Stone","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Ayanful-Torgby, R., Sarpong, E., Abagna, H.B., Donu, D., Obboh, E., Mensah, B.A., Adjah, J., Williamson, K.C., and Amoah, L.E. (2021). Persistent Plasmodium falciparum Infections Enhance Transmission-Reducing Immunity Development. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00973-5"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4049\/jimmunol.138.1.306","article-title":"Human T Clones Reactive to the Sexual Stages of Plasmodium falciparum Malaria. High Frequency of Gamete-Reactive T Cells in Peripheral Blood from Nonexposed Donors","volume":"138","author":"Good","year":"1987","journal-title":"J. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0165-2478(90)90095-8","article-title":"Plasmodium falciparum Sexual Stage Antigens: Immunogenicity and Cell-Mediated Responses","volume":"25","author":"Targett","year":"1990","journal-title":"Immunol. Lett."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1046\/j.1365-3024.1997.d01-238.x","article-title":"Polyclonal T-Cell Responses to Plasmodium falciparum Gametocytes in Malaria Nonexposed Donors","volume":"19","author":"Goodier","year":"1997","journal-title":"Parasite Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/imm.12621","article-title":"Reduced Immunogenicity of Plasmodium falciparum Gamete Surface Antigen (Pfs48\/45) in Mice after Disruption of Disulphide Bonds\u2014Evaluating Effect of Interferon-\u03b3-Inducible Lysosomal Thiol Reductase","volume":"148","author":"Merino","year":"2016","journal-title":"Immunology"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/5\/423\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:19:03Z","timestamp":1778386743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/5\/423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":122,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["vaccines14050423"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14050423","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]}}}