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Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here, we compare four distinct full-length<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>CS proteins expressed in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>or<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pichia pastoris<\/jats:named-content>for their ability to induce immunity and protection in mice when administered with long-chain poly(I\u00b7C) [poly(I\u00b7C)LC] as an adjuvant. CS proteins expressed in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>induced high-titer antibody responses against the NANP repeat region and potent CSP-specific CD4<jats:sup>+<\/jats:sup>T cell responses. Moreover,<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>-derived CS proteins in combination with poly(I\u00b7C)LC induced potent multifunctional (interleukin 2-positive [IL-2<jats:sup>+<\/jats:sup>], tumor necrosis factor alpha-positive [TNF-\u03b1<jats:sup>+<\/jats:sup>], gamma interferon-positive [IFN-\u03b3<jats:sup>+<\/jats:sup>]) CD4<jats:sup>+<\/jats:sup>effector T cell responses in blood, in spleen, and particularly in liver. Using transgenic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium berghei<\/jats:named-content>expressing the repeat region of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>CSP [<jats:italic>Pb<\/jats:italic>-CS(<jats:italic>Pf<\/jats:italic>)], we showed that there was a 1- to 4-log decrease in malaria rRNA in the liver following a high-dose challenge and \u223c50% sterilizing protection with a low-dose challenge compared to control levels. Protection was directly correlated with high-level antibody titers but not CD4<jats:sup>+<\/jats:sup>T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4<jats:sup>+<\/jats:sup>T cell immunity that was significantly less potent than that with poly(I\u00b7C)LC. Overall, these data suggest that full-length CS proteins and poly(I\u00b7C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection.<\/jats:p>","DOI":"10.1128\/iai.01108-12","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T04:55:08Z","timestamp":1356756908000},"page":"789-800","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I\u00b7C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4<sup>+<\/sup>T Cell Immunity and Protection in Mice"],"prefix":"10.1128","volume":"81","author":[{"given":"Kathrin","family":"Kastenm\u00fcller","sequence":"first","affiliation":[{"name":"Vaccine Research Center and Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Trager","sequence":"additional","affiliation":[{"name":"Vaccine Research Center and Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"},{"name":"Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Stoyanov","sequence":"additional","affiliation":[{"name":"Vaccine Research Center and Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"},{"name":"Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Salazar","sequence":"additional","affiliation":[{"name":"Oncovir, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Pokalwar","sequence":"additional","affiliation":[{"name":"Gennova Biopharmaceuticals Ltd., Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Singh","sequence":"additional","affiliation":[{"name":"Gennova Biopharmaceuticals Ltd., Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetij","family":"Dutta","sequence":"additional","affiliation":[{"name":"Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F.","family":"Ockenhouse","sequence":"additional","affiliation":[{"name":"Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidel","family":"Zavala","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Seder","sequence":"additional","affiliation":[{"name":"Vaccine Research Center and Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2011. 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