{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:44:11Z","timestamp":1793835851614,"version":"4.6.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["AI47089"],"award-info":[{"award-number":["AI47089"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007108","name":"George Washington University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infective stage and sexual\/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.\n                  <\/jats:p>","DOI":"10.1038\/s41541-022-00577-8","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T08:02:14Z","timestamp":1669881734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum"],"prefix":"10.1038","volume":"7","author":[{"given":"Clifford T. 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Hum. Vaccin Immunother. 16, 480\u2013489 (2020).","journal-title":"Hum. Vaccin Immunother."},{"key":"577_CR6","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.3389\/fimmu.2019.02412","volume":"10","author":"Y Yusuf","year":"2019","unstructured":"Yusuf, Y. et al. A viral-vectored multi-stage malaria vaccine regimen with protective and transmission-blocking efficacies. Front Immunol. 10, 2412 (2019).","journal-title":"Front Immunol."},{"key":"577_CR7","doi-asserted-by":"publisher","first-page":"e0131456","DOI":"10.1371\/journal.pone.0131456","volume":"10","author":"A Boes","year":"2015","unstructured":"Boes, A. et al. Analysis of a multi-component multi-stage malaria vaccine candidate-tackling the cocktail challenge. PLoS One 10, e0131456 (2015).","journal-title":"PLoS One"},{"key":"577_CR8","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1002\/biot.201500055","volume":"10","author":"H Spiegel","year":"2015","unstructured":"Spiegel, H. et al. The stage-specific in vitro efficacy of a malaria antigen cocktail provides valuable insights into the development of effective multi-stage vaccines. Biotechnol. J. 10, 1651\u20131659 (2015).","journal-title":"Biotechnol. J."},{"key":"577_CR9","doi-asserted-by":"publisher","unstructured":"Brod, F. et al. Combination of RTS,S and Pfs25-IMX313 induces a functional antibody response against malaria infection and transmission in mice. Front. Immunol. 9 https:\/\/doi.org\/10.3389\/fimmu.2018.02780 (2018).","DOI":"10.3389\/fimmu.2018.02780"},{"key":"577_CR10","doi-asserted-by":"publisher","first-page":"26951","DOI":"10.1074\/jbc.M109.013706","volume":"284","author":"ML Plassmeyer","year":"2009","unstructured":"Plassmeyer, M. L. et al. Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate. J. Biol. Chem. 284, 26951\u201326963 (2009).","journal-title":"J. Biol. 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N.K. and D.W. are named as inventors on a provisional patent application filed by the George Washington University. P.L. and Y.T. are employees of Acuitas Therapeutics, a company involved in the development of mRNA-LNP therapeutics. D.W., and M.-G.A. are named on patents that describe lipid nanoparticles for delivery of nucleic acid therapeutics, including mRNA and the use of modified mRNA in lipid nanoparticles as a vaccine platform.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"155"}}