{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:08:40Z","timestamp":1785420520284,"version":"3.56.0"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["ZIA AI000892-23"],"award-info":[{"award-number":["ZIA AI000892-23"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Malaria is a complex parasitic disease caused by species of <jats:italic>Plasmodium<\/jats:italic> parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement. Some issues associated with the difficulties in developing a sterile vaccine include high antigenic diversity, switching expression of the immune targets, and inhibition of immune pathways. Current vaccine research focuses on identifying conserved and protective epitopes, developing multivalent vaccines (including the whole parasite), and using more powerful adjuvants. However, overcoming the systematic immune inhibition and immune cell dysfunction\/exhaustion may be required before high titers of protective antibodies can be achieved. Increased expression of surface molecules such as CD86 and MHC II on antigen-presenting cells and blocking immune checkpoint pathways (interactions of PD-1 and PD-L1; CTLA-4 and CD80) using small molecules could be a promising approach for enhancing vaccine efficacy. This assay reviews the factors affecting the disease severity, the genetics of host\u2013parasite interaction, immune evasion mechanisms, and approaches potentially to improve host immune response for vaccine development.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012853","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T18:26:26Z","timestamp":1737656786000},"page":"e1012853","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3246-3248","authenticated-orcid":true,"given":"Xin-zhuan","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel V.","family":"Stadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awet Alem","family":"Teklemichael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"issue":"1","key":"ppat.1012853.ref001","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41598-018-36493-y","article-title":"Genetically diverse Plasmodium falciparum infections, within-host competition and symptomatic malaria in humans","volume":"9","author":"P Sondo","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"ppat.1012853.ref002","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1179\/136485910X12607012373876","article-title":"Genetic diversity of Plasmodium falciparum in Bolifamba, on the slopes of Mount Cameroon: influence of MSP1 allelic variants on symptomatic malaria and anaemia","volume":"104","author":"DN 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