{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:55:45Z","timestamp":1761155745171},"reference-count":69,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Immunization with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>sporozoites can elicit high levels of sterile immunity, and neutralizing antibodies from protected hosts are known to target the repeat region of the circumsporozoite (CS) protein on the parasite surface. CS-based subunit vaccines have been hampered by suboptimal immunogenicity and the requirement for strong adjuvants to elicit effective humoral immunity. Pathogen-associated molecular patterns (PAMPs) that signal through Toll-like receptors (TLRs) can function as potent adjuvants for innate and adaptive immunity. We examined the immunogenicity of recombinant proteins containing a TLR5 agonist, flagellin, and either full-length or selected epitopes of the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>CS protein. Mice immunized with either of the flagellin-modified CS constructs, administered intranasally (i.n.) or subcutaneously (s.c.), developed similar levels of malaria-specific IgG1 antibody and interleukin-5 (IL-5)-producing T cells. Importantly, immunization via the i.n. but not the s.c. route elicited sporozoite neutralizing antibodies capable of inhibiting &gt;90% of sporozoite invasion<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>, as measured using a transgenic rodent parasite expressing<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>CS repeats. These findings demonstrate that functional sporozoite neutralizing antibody can be elicited by i.n. immunization with a flagellin-modified<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>CS protein and raise the potential of a scalable, safe, needle-free vaccine for the 40% of the world's population at risk of malaria.<\/jats:p>","DOI":"10.1128\/iai.00263-13","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T03:04:40Z","timestamp":1379387080000},"page":"4350-4362","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin"],"prefix":"10.1128","volume":"81","author":[{"given":"Daniel","family":"Carapau","sequence":"first","affiliation":[{"name":"Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, USA"}]},{"given":"Robert","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, USA"}]},{"given":"Ad\u00e9la","family":"Nacer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, USA"}]},{"given":"Alan","family":"Shaw","sequence":"additional","affiliation":[{"name":"Vaxinnate Corporation, Cranbury, New Jersey, USA"}]},{"given":"Caroline","family":"Othoro","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, USA"}]},{"given":"Ute","family":"Frevert","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, USA"}]},{"given":"Elizabeth","family":"Nardin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, USA"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/216160a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1975.24.397"},{"key":"e_1_3_3_4_2","first-page":"9","article-title":"Immunity to falciparum and vivax malaria induced by irradiated sporozoites: a review of the University of Maryland studies, 1971\u201375","volume":"68","author":"Clyde DF","year":"1990","unstructured":"ClydeDF. 1990. 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