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A major limitation of the currently licensed pneumococcal vaccines is the lack of efficacy against mucosal disease manifestations such as AOM, acute bacterial sinusitis and pneumonia. We sought to generate a novel class of live vaccines that (1) retain all major antigenic virulence proteins yet are fully attenuated and (2) protect against otitis media. A live vaccine candidate based on deletion of the signal recognition pathway component\n                    <jats:italic>ftsY<\/jats:italic>\n                    induced potent, serotype\u2010independent protection against otitis media, sinusitis, pneumonia and invasive pneumococcal disease. Protection was maintained in animals coinfected with influenza virus, but was lost if mice were depleted of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells at the time of vaccination. The live vaccine induced a strong serum IgG2a and IgG2b response that correlated with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell mediated class switching. Deletion of genes required for microbial adaptation to the host environment is a novel live attenuated vaccine strategy yielding the first experimental vaccine effective against pneumococcal otitis media.\n                  <\/jats:p>","DOI":"10.1002\/emmm.201202150","type":"journal-article","created":{"date-parts":[[2013,11,4]],"date-time":"2013-11-04T05:10:41Z","timestamp":1383541841000},"page":"141-154","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A live\u2010attenuated pneumococcal vaccine elicits CD4+ T\u2010cell dependent class switching and provides serotype independent protection against acute otitis media"],"prefix":"10.1038","volume":"6","author":[{"given":"Jason W","family":"Rosch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy R","family":"Iverson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Humann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Mann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geli","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Mina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle A","family":"Murrah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia C","family":"Perez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Edward Swords","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine I","family":"Tuomanen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A","family":"McCullers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,11,4]]},"reference":[{"key":"BFEMMM201202150_CR1","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1128\/iai.62.12.5683-5688.1994","volume":"62","author":"JE Alexander","year":"1994","unstructured":"Alexander JE, Lock RA, Peeters CC, Poolman JT, Andrew PW, Mitchell TJ, Hansman D, Paton JC (1994) Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. 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