Identifying Plasmodium P36 and P52 antigens for co-administration with circumsporozoite protein to enhance vaccine efficacy

Identifying Plasmodium P36 and P52 antigens for co-administration with circumsporozoite protein to enhance vaccine efficacy | 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 Identifying Plasmodium P36 and P52 antigens for co-administration with circumsporozoite protein to enhance vaccine efficacy Sean Murphy, Naveen Yadav, Anya Kalata, Rebekah Reynolds, Andrew Raappana, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4909396/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Dec, 2024 Read the published version in npj Vaccines → Version 1 posted 12 You are reading this latest preprint version Abstract Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP. Co-administration of P36 and/or P52 with CSP achieved 80-100% sterile protection in mice, compared to only 7-30% protection for each individual antigen. P36 and P52 vaccination induced murine CD4+ and CD8+ T cell responses, but not antibody responses. This study adds P36 and P52 as promising vaccine antigens that may enhance protection achieved by CSP vaccination. Biological sciences/Immunology/Applied immunology/Vaccines/DNA vaccines Biological sciences/Immunology/Infectious diseases/Malaria Plasmodium yoelii Radiation and genetically attenuated sporozoites CD8+ T cells CD4+ T cells malaria vaccine circumsporozoite protein (CSP) P36 P52 Full Text Additional Declarations There is a conflict of interest NY and SCM have ownership interest in provisional patent filed for P36 and P52 proteins (Application # PCT/US24/16044). Supplementary Files SupplementaryInformationYadavetal.pdf Cite Share Download PDF Status: Published Journal Publication published 06 Dec, 2024 Read the published version in npj Vaccines → Version 1 posted Editorial decision: revise 24 Sep, 2024 Review # 3 received at journal 20 Sep, 2024 Review # 2 received at journal 30 Aug, 2024 Review # 1 received at journal 29 Aug, 2024 Reviewer # 3 agreed at journal 28 Aug, 2024 Reviewer # 2 agreed at journal 27 Aug, 2024 Reviewer # 1 agreed at journal 23 Aug, 2024 Reviewers invited by journal 23 Aug, 2024 Editor assigned by journal 21 Aug, 2024 Submission checks completed at journal 16 Aug, 2024 First submitted to journal 14 Aug, 2024 Unknown event 14 Aug, 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. 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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-4909396","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":344252383,"identity":"63804ead-2977-469a-96e2-e88959301bd7","order_by":0,"name":"Sean Murphy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYJACZhDBD2aykaJFsoFkLQYHiNWiOyP32ePCtjp54xs5Bgwfyg4T1mJ2I93ceGbbYcNtQC2MM84RpSWNTZq37UCC2Y3cDcy8bcRrqUswngHU8pcELcwJBhJALYxEaTnzjN2Y59xhwxln3n842HMunQgtx9PYHvOU1cnzt6clPvhRZk1YCwMoLhih0XGAKPVgLQx/iFU7CkbBKBgFIxIAAH06OG4Rc/3pAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-2048-0131","institution":"University of Washington","correspondingAuthor":true,"prefix":"","firstName":"Sean","middleName":"","lastName":"Murphy","suffix":""},{"id":344252384,"identity":"1b7cee0b-cec6-4018-9e4a-5200bf66642a","order_by":1,"name":"Naveen Yadav","email":"","orcid":"","institution":"University of Washington","correspondingAuthor":false,"prefix":"","firstName":"Naveen","middleName":"","lastName":"Yadav","suffix":""},{"id":344252385,"identity":"852966f7-ff2a-418c-8df5-d8752972007e","order_by":2,"name":"Anya Kalata","email":"","orcid":"","institution":"University of Washington","correspondingAuthor":false,"prefix":"","firstName":"Anya","middleName":"","lastName":"Kalata","suffix":""},{"id":344252386,"identity":"3374fd4f-804e-4201-9cc8-98702c9c276d","order_by":3,"name":"Rebekah Reynolds","email":"","orcid":"","institution":"University of Washington","correspondingAuthor":false,"prefix":"","firstName":"Rebekah","middleName":"","lastName":"Reynolds","suffix":""},{"id":344252387,"identity":"23a391e7-ba3e-42dd-a10d-794ab222a580","order_by":4,"name":"Andrew Raappana","email":"","orcid":"","institution":"Seattle Children's Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Raappana","suffix":""},{"id":344252388,"identity":"109b62b5-40b8-4da7-8218-09397b927987","order_by":5,"name":"Noah Sather","email":"","orcid":"https://orcid.org/0000-0002-9128-172X","institution":"Seattle Childrens","correspondingAuthor":false,"prefix":"","firstName":"Noah","middleName":"","lastName":"Sather","suffix":""}],"badges":[],"createdAt":"2024-08-13 20:55:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4909396/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4909396/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41541-024-01040-6","type":"published","date":"2024-12-06T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70817159,"identity":"ded680d1-4a10-425d-9457-cf66d4e7b534","added_by":"auto","created_at":"2024-12-07 08:08:18","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2662612,"visible":true,"origin":"","legend":"Article File","description":"","filename":"P52andP36ManuscriptYadavetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4909396/v1_covered_44d4f937-1533-4829-b390-19e7c705893c.pdf"},{"id":65192112,"identity":"641808a5-ac3f-4db2-84e9-5555067ae425","added_by":"auto","created_at":"2024-09-24 14:48:15","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":769907,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformationYadavetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4909396/v1/e0de2727d0c6a0c53bf69a18.pdf"}],"financialInterests":"There is a conflict of interest\nNY and SCM have ownership interest in provisional patent filed for P36 and P52 proteins (Application # 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