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Needle-free vaccination strategies are desirable, yet most PfCSP-targeted vaccines like RTS,S require needle-based administration. Here, we evaluated the edible algae, <jats:italic>Arthrospira platensis<\/jats:italic> (commonly called \u2018spirulina\u2019) as a malaria vaccine platform. Spirulina were genetically engineered to express virus-like particles (VLPs) consisting of the woodchuck hepatitis B core capsid protein (WHcAg) displaying a (NANP)<jats:sub>15<\/jats:sub> PfCSP antigen on its surface. PfCSP-spirulina administered to mice intranasally followed by oral PfCSP-spirulina boosters resulted in a strong, systemic anti-PfCSP immune response that was protective against subcutaneous challenge with PfCSP-expressing <jats:italic>P. yoelii<\/jats:italic>. Unlike male mice, female mice did not require Montanide adjuvant to reach high antibody titers or protection. The successful use of spirulina as a vaccine delivery system warrants further development of spirulina-based vaccines as a useful tool in addressing malaria and other diseases of global health importance.<\/jats:p>","DOI":"10.1038\/s41541-022-00534-5","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T10:03:39Z","timestamp":1664877819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Needle-free, spirulina-produced Plasmodium falciparum circumsporozoite vaccination provides sterile protection against pre-erythrocytic malaria in mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Tracy","family":"Saveria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaitra","family":"Parthiban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette M.","family":"Seilie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Brady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anissa","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridhima","family":"Manocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esha","family":"Afreen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Krzeszowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Paddock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad C.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tasch","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"}]}],"member":"297","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"534_CR1","unstructured":"World Health Organization. 2021. 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