{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:19:20Z","timestamp":1790176760579,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Conjugate vaccines consisting of the capsular polysaccharide (PS) of Haemophilus influenzae type b (Hib) covalently linked to carrier proteins, unlike pure PS, are immunogenic in infants and have significantly reduced Hib infections in the United States, but require multiple doses to induce protective anti-PS Ab titers. Hib-meningococcal outer membrane protein complex (OMPC) conjugate vaccine, however, elicits protective anti-PS Ab titers after one dose. We found that OMPC and Hib-OMPC engaged human Toll-like receptor 2 (TLR2) expressed in human embryonic kidney (HEK) cells, inducing IL-8 production, and engaged mouse TLR2 on bone marrow-derived dendritic cells, inducing TNF release. Hib conjugated to the carrier proteins CRM197 and tetanus toxoid did not engage TLR2 on HEK or dendritic cells. Engagement of TLR2 by Hib-OMPC was MyD88 dependent, as Hib-OMPC-induced TNF production was ablated in MyD88 knockout (KO) mice. Hib-OMPC was significantly less immunogenic in TLR2 KO mice, inducing lower Hib PS IgG and IgM titers compared with those in wild-type mice. Splenocytes from OMPC-immunized TLR2 KO mice also produced significantly less IL-6 and TNF-\u03b1 than those from wild-type mice. Hib-OMPC is unique among glycoconjugate vaccines by engaging TLR2, and the ability of Hib-OMPC to elicit protective levels of Abs after one dose may be related to TLR2-mediated induction and regulation of cytokines produced by T cells and macrophages in addition to the peptide\/MHC II-dependent recruitment of T cell help commonly afforded by carrier proteins. TLR2 engagement by an adjuvant or carrier protein may be a useful strategy for augmentation of the anti-PS Ab response induced by glycoconjugate vaccines.<\/jats:p>","DOI":"10.4049\/jimmunol.172.4.2431","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T23:33:57Z","timestamp":1398209637000},"page":"2431-2438","source":"Crossref","is-referenced-by-count":96,"title":["<i>Haemophilus influenzae<\/i>\n                    Type b-Outer Membrane Protein Complex Glycoconjugate Vaccine Induces Cytokine Production by Engaging Human Toll-Like Receptor 2 (TLR2) and Requires the Presence of TLR2 for Optimal Immunogenicity"],"prefix":"10.1093","volume":"172","author":[{"given":"Eicke","family":"Latz","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Franko","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Pathology, Case Western Reserve University , Cleveland OH 44106"},{"name":"Division of Infectious Diseases, Rainbow Babies and Children\u2019s Hospital , Cleveland OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas T","family":"Golenbock","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Pathology, Case Western Reserve University , Cleveland OH 44106"},{"name":"Division of Infectious Diseases, Rainbow Babies and Children\u2019s Hospital , Cleveland OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,2,15]]},"reference":[{"key":"2026020211200174300_R1","first-page":"65","volume-title":"Annu. 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