The effect of the RTS,S/AS01E vaccine booster dose on cell-mediated immune responses in African infants and children

The effect of the RTS,S/AS01E vaccine booster dose on cell-mediated immune responses in African infants and children | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The effect of the RTS,S/AS01E vaccine booster dose on cell-mediated immune responses in African infants and children Gemma Moncunill, Robert Mitchell, Dídac Macià, Chenjerai Jairoce, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4390542/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Oct, 2024 Read the published version in npj Vaccines → Version 1 posted 9 You are reading this latest preprint version Abstract RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunizations and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in lymphocytes from 709 children and infants following RTS,S/AS01E antigen stimulation, which were assessed for associations with malaria risk and antibodies one month post-booster and one year later. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E vaccination after booster, and IL-2 responses to circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one cohort, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy. Health sciences/Diseases/Infectious diseases/Malaria Biological sciences/Immunology/Adaptive immunity/Cellular immunity/Lymphocyte activation malaria vaccine booster cytokines antibodies cellular immune responses immunity Full Text Additional Declarations There is a conflict of interest JJC is employed by Antigen Discovery Inc., Irvine, CA, United States, but declares no financial or non-financial competing interests. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be seen as a potential conflict of interest. Supplementary Files MitchellNPJVACCINES04060SupplementaryFigures.pdf Cite Share Download PDF Status: Published Journal Publication published 25 Oct, 2024 Read the published version in npj Vaccines → Version 1 posted Editorial decision: revise 06 Jun, 2024 Review # 2 received at journal 05 Jun, 2024 Review # 1 received at journal 05 Jun, 2024 Reviewer # 2 agreed at journal 22 May, 2024 Reviewer # 1 agreed at journal 20 May, 2024 Reviewers invited by journal 20 May, 2024 Editor assigned by journal 14 May, 2024 Submission checks completed at journal 09 May, 2024 First submitted to journal 08 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4390542","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":302539448,"identity":"d2bfc51c-5626-483b-8a94-47ee973809fa","order_by":0,"name":"Gemma Moncunill","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0001-5105-9836","institution":"ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona","correspondingAuthor":true,"prefix":"","firstName":"Gemma","middleName":"","lastName":"Moncunill","suffix":""},{"id":302539449,"identity":"917fd2d0-4278-4188-bc58-3bfaf3733d7f","order_by":1,"name":"Robert Mitchell","email":"","orcid":"https://orcid.org/0000-0003-0424-7257","institution":"ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Mitchell","suffix":""},{"id":302539450,"identity":"6f1fb731-1169-465f-884c-adcf4f6f6cdf","order_by":2,"name":"Dídac Macià","email":"","orcid":"","institution":"Barcelona Institute for Global Health (ISGlobal)","correspondingAuthor":false,"prefix":"","firstName":"Dídac","middleName":"","lastName":"Macià","suffix":""},{"id":302539451,"identity":"2ee7a814-0b57-4c06-9b02-99fd98104519","order_by":3,"name":"Chenjerai Jairoce","email":"","orcid":"","institution":"Manhiça Health Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Chenjerai","middleName":"","lastName":"Jairoce","suffix":""},{"id":302539452,"identity":"f19db2f2-a281-45ea-b969-6c02e04d82eb","order_by":4,"name":"Maxmillian Mpina","email":"","orcid":"","institution":"Ifakara Health Institute. Bagamoyo Research and Training Centre","correspondingAuthor":false,"prefix":"","firstName":"Maxmillian","middleName":"","lastName":"Mpina","suffix":""},{"id":302539453,"identity":"cfbda378-c97f-4b69-bd67-5a7da9e868c5","order_by":5,"name":"Akshayata Naidu","email":"","orcid":"https://orcid.org/0000-0001-8958-2622","institution":"ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Catalonia, Spain.","correspondingAuthor":false,"prefix":"","firstName":"Akshayata","middleName":"","lastName":"Naidu","suffix":""},{"id":302539454,"identity":"bf2dfadb-586d-41f9-b82e-0ae6a2e051ed","order_by":6,"name":"Ana Chopo-Pizarro","email":"","orcid":"https://orcid.org/0000-0002-4330-4085","institution":"ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Catalonia, Spain.","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Chopo-Pizarro","suffix":""},{"id":302539455,"identity":"17aa57e2-c5f6-4c45-90f3-5e338451d82f","order_by":7,"name":"Miquel Vázquez-Santiago","email":"","orcid":"","institution":"ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Catalonia, Spain.","correspondingAuthor":false,"prefix":"","firstName":"Miquel","middleName":"","lastName":"Vázquez-Santiago","suffix":""},{"id":302539456,"identity":"9c8b8a58-6eaa-4bd5-9ec6-7e7d331e26df","order_by":8,"name":"Joseph Campo","email":"","orcid":"","institution":"Barcelona Institute for Global Health","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Campo","suffix":""},{"id":302539457,"identity":"1958c0b5-681a-41cc-9261-dc3fa90d60a6","order_by":9,"name":"Pedro Aide","email":"","orcid":"https://orcid.org/0000-0002-2379-6529","institution":"Manhiça Health Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"","lastName":"Aide","suffix":""},{"id":302539458,"identity":"b24325af-e287-4265-84d1-e1d600af0c88","order_by":10,"name":"Claudia Daubenberger","email":"","orcid":"","institution":"Swiss Tropical and Public Health Institute, Basel, Switzerland","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Daubenberger","suffix":""},{"id":302539459,"identity":"584f4f11-d39e-435a-a2bd-0c1478f9e70e","order_by":11,"name":"Carlota Dobaño","email":"","orcid":"https://orcid.org/0000-0002-6751-4060","institution":"Barcelona Institute for Global Health (ISGlobal)","correspondingAuthor":false,"prefix":"","firstName":"Carlota","middleName":"","lastName":"Dobaño","suffix":""}],"badges":[],"createdAt":"2024-05-08 16:14:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4390542/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4390542/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41541-024-00977-y","type":"published","date":"2024-10-25T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67530092,"identity":"8a867928-1fcf-41e5-8eb9-d37e935d5681","added_by":"auto","created_at":"2024-10-26 07:05:49","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1670996,"visible":true,"origin":"","legend":"","description":"","filename":"MitchellNPJVACCINES04060.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4390542/v1_covered_58b97d0a-8504-4dfe-a85c-c63f92e32000.pdf"},{"id":56499767,"identity":"7dd51f9e-ea01-41a2-a43f-7abe163de5c8","added_by":"auto","created_at":"2024-05-15 03:33:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3303265,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"MitchellNPJVACCINES04060SupplementaryFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4390542/v1/066d7a61d15bd81c05e9efc0.pdf"}],"financialInterests":"There is a conflict of interest\nJJC is employed by Antigen Discovery Inc., Irvine, CA, United States, but declares no financial or non-financial competing interests. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be seen as a potential conflict of interest.","formattedTitle":"The effect of the RTS,S/AS01E vaccine booster dose on cell-mediated immune responses in African infants and children","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"npj-vaccines","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjvaccines","sideBox":"Learn more about [npj Vaccines](http://www.nature.com/npjvaccines/)","snPcode":"41541","submissionUrl":"https://submission.springernature.com/new-submission/41541/3?","title":"npj Vaccines","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"malaria, vaccine, booster, cytokines, antibodies, cellular immune responses, immunity","lastPublishedDoi":"10.21203/rs.3.rs-4390542/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4390542/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunizations and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in lymphocytes from 709 children and infants following RTS,S/AS01E antigen stimulation, which were assessed for associations with malaria risk and antibodies one month post-booster and one year later. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E vaccination after booster, and IL-2 responses to circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one cohort, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.","manuscriptTitle":"The effect of the RTS,S/AS01E vaccine booster dose on cell-mediated immune responses in African infants and children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-15 03:33:04","doi":"10.21203/rs.3.rs-4390542/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-06-06T13:10:41+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-06-05T06:00:45+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-06-05T04:01:10+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-05-22T11:58:45+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-05-20T14:50:27+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-05-20T14:28:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-15T00:19:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-09T08:41:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"npj Vaccines","date":"2024-05-08T15:48:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"npj-vaccines","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjvaccines","sideBox":"Learn more about [npj Vaccines](http://www.nature.com/npjvaccines/)","snPcode":"41541","submissionUrl":"https://submission.springernature.com/new-submission/41541/3?","title":"npj Vaccines","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3fd4dc98-ec3d-4991-b216-7dc70e106fa3","owner":[],"postedDate":"May 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31922832,"name":"Health sciences/Diseases/Infectious diseases/Malaria"},{"id":31922833,"name":"Biological sciences/Immunology/Adaptive immunity/Cellular immunity/Lymphocyte activation"}],"tags":[],"updatedAt":"2024-10-26T07:05:42+00:00","versionOfRecord":{"articleIdentity":"rs-4390542","link":"https://doi.org/10.1038/s41541-024-00977-y","journal":{"identity":"npj-vaccines","isVorOnly":false,"title":"npj Vaccines"},"publishedOn":"2024-10-25 04:00:00","publishedOnDateReadable":"October 25th, 2024"},"versionCreatedAt":"2024-05-15 03:33:04","video":"","vorDoi":"10.1038/s41541-024-00977-y","vorDoiUrl":"https://doi.org/10.1038/s41541-024-00977-y","workflowStages":[]},"version":"v1","identity":"rs-4390542","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4390542","identity":"rs-4390542","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}