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Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8\u2009+\u2009T-cell responses sufficient for long-term protection. In contrast, whole-organism (WO) vaccines, such as Radiation Attenuated Sporozoites (RAS), achieved sterile protection but require a series of intravenous doses administered in multiple clinic visits. Moreover, these WO vaccines must be produced in mosquitos, a burdensome process that severely limits their availability. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. The priming dose is a single dose of self-replicating RNA encoding the full-length\n                    <jats:italic>P. yoelii<\/jats:italic>\n                    CS protein, delivered via an advanced cationic nanocarrier (LION\n                    <jats:sup>TM<\/jats:sup>\n                    ). The trapping dose consists of one dose of WO RAS. Our vaccine induces a strong immune response when administered in an accelerated regimen, i.e., either 5-day or same-day immunization. Additionally, mice after same-day immunization showed a 2-day delay of blood patency with 90% sterile protection against a 3-week spz challenge. The same-day regimen also induced durable 70% sterile protection against a 2-month spz challenge. Our approach presents a clear path to late-stage preclinical and clinical testing of dose-sparing, same-day regimens that can confer sterilizing protection against malaria.\n                  <\/jats:p>","DOI":"10.1038\/s41541-023-00799-4","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T14:02:03Z","timestamp":1704895323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine"],"prefix":"10.1038","volume":"9","author":[{"given":"Zachary","family":"MacMillen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiara","family":"Hatzakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie J.","family":"Shears","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse H.","family":"Erasmus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit P.","family":"Khandhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5577-7787","authenticated-orcid":false,"given":"Brandon","family":"Wilder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-0131","authenticated-orcid":false,"given":"Sean C.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Davie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-2049","authenticated-orcid":false,"given":"Marion","family":"Avril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"799_CR1","unstructured":"WHO | World malaria report 2018. 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M.A. and Z.M. are co-inventors on international patent PCT\/US2023\/19674. J.D. has equity interests in MalarVx, Inc. A.S., J.H.E., A.P.K. and S.G.R. are full-time employees of HDT Bio. A.S., J.H.E., A.P.K and S.G.R. have equity interests in HDT Bio. J.H.E has consulting agreements with various life sciences companies. J.H.E. and A.P.K. are inventors on granted U.S. patents pertaining to HDT Bio\u2019s proprietary cationic nanocarrier formulation. S. C. M. has a patent application on selected aspects of the prime-and-trap concept through the University of Washington and has equity in a startup company (Sound Vaccines, Inc.) that is negotiating with the University of Washington for rights to this intellectual property. All other authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}