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Furthermore, we recently demonstrated that intranasal immunization with an Fc\u03b3R-targeted antigen enhances protection against a category A intracellular mucosal pathogen,<jats:named-content content-type=\"genus-species\">Francisella tularensis<\/jats:named-content>. To determine if a similar strategy could be applied to the important pathogen<jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>, we used an improved mucosal FcR-targeting strategy that specifically targets human Fc\u03b3R type I (hFc\u03b3RI). A humanized single-chain antibody component in which the variable domain binds to hFc\u03b3RI [anti-hFc\u03b3RI (H22)] was linked in a fusion protein with the pneumococcal surface protein A (PspA). PspA is known to elicit protection against pneumococcal sepsis, carriage, and pneumonia in mouse models when administered with adjuvants. Anti-hFc\u03b3RI-PspA or recombinant PspA (rPspA) alone was used to intranasally immunize wild-type (WT) and hFc\u03b3RI transgenic (Tg) mice in the absence of adjuvant. The hFc\u03b3RI Tg mice receiving anti-hFc\u03b3RI-PspA exhibited elevated<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>-specific IgA, IgG2c, and IgG1 antibodies in serum and bronchoalveolar lavage fluid. Neither immunogen was effective in protecting WT mice in the absence of adjuvant, but when PspA was targeted to hFc\u03b3RI as the anti-hFc\u03b3RI-PspA fusion, enhanced protection against lethal<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>challenge was observed in the hFc\u03b3RI Tg mice compared to mice given nontargeted rPspA alone. Immune sera from the anti-hFc\u03b3RI-PspA-immunized Tg mice showed enhanced complement C3 deposition on bacterial surfaces, and protection was dependent upon an active complement system. Immune serum also showed an enhanced bactericidal activity directed against<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>that appears to be lactoferrin mediated.<\/jats:p>","DOI":"10.1128\/iai.05511-11","type":"journal-article","created":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T04:52:32Z","timestamp":1323751952000},"page":"1166-1180","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Mucosal Immunization with an Unadjuvanted Vaccine That Targets Streptococcus pneumoniae PspA to Human Fc\u03b3 Receptor Type I Protects against Pneumococcal Infection through Complement- and Lactoferrin-Mediated Bactericidal Activity"],"prefix":"10.1128","volume":"80","author":[{"given":"Constantine","family":"Bitsaktsis","sequence":"first","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibiana V.","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus","family":"Colino","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford M.","family":"Snapper","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan K.","family":"Hollingshead","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giang","family":"Pham","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane R.","family":"Gosselin","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund J.","family":"Gosselin","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/08820130500265372"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.2.562"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.11.6718-6724.2001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24772"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.796-800.2000"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.1.111-116.1992"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(99)00511-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/317602"},{"key":"e_1_3_3_10_2","volume-title":"Pneumococcal vaccines: impact of the conjugate vaccine.","author":"Briles DE","year":"2008","unstructured":"Briles DE, Jonsdottir I, Hollingshead SK. 2008. 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