{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:40:31Z","timestamp":1787586031027,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The Malaria Vaccine Technology Roadmap 2013 (World Health Organization) aims to develop safe and effective vaccines by 2030 that will offer at least 75% protective efficacy against clinical malaria and reduce parasite transmission. Here, we demonstrate a highly effective multistage vaccine against both the pre-erythrocytic and sexual stages of <jats:italic>Plasmodium falciparum<\/jats:italic> that protects and reduces transmission in a murine model. The vaccine is based on a viral-vectored vaccine platform, comprising a highly-attenuated vaccinia virus strain, LC16m8\u0394 (m8\u0394), a genetically stable variant of a licensed and highly effective Japanese smallpox vaccine LC16m8, and an adeno-associated virus (AAV), a viral vector for human gene therapy. The genes encoding <jats:italic>P. falciparum<\/jats:italic> circumsporozoite protein (PfCSP) and the ookinete protein P25 (Pfs25) are expressed as a Pfs25\u2013PfCSP fusion protein, and the heterologous m8\u0394-prime\/AAV-boost immunization regimen in mice provided both 100% protection against PfCSP-transgenic <jats:italic>P. berghei<\/jats:italic> sporozoites and up to 100% transmission blocking efficacy, as determined by a direct membrane feeding assay using parasites from <jats:italic>P. falciparum<\/jats:italic>-positive, naturally-infected donors from endemic settings. Remarkably, the persistence of vaccine-induced immune responses were over 7 months and additionally provided complete protection against repeated parasite challenge in a murine model. We propose that application of the m8\u0394\/AAV malaria multistage vaccine platform has the potential to contribute to the landmark goals of the malaria vaccine technology roadmap, to achieve life-long sterile protection and high-level transmission blocking efficacy.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1005476","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T14:56:33Z","timestamp":1664463393000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study"],"prefix":"10.3389","volume":"13","author":[{"given":"Mitsuhiro","family":"Iyori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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