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Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intact<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>elicits murine CD4<jats:sup>+<\/jats:sup>T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responses<jats:italic>in vivo<\/jats:italic>. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of live<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content><jats:italic>in vitro<\/jats:italic>. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremia<jats:italic>in vivo<\/jats:italic>relative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid.<\/jats:p>","DOI":"10.1128\/iai.00271-13","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T04:00:00Z","timestamp":1367899200000},"page":"2554-2561","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Novel Synthetic (Poly)Glycerolphosphate-Based Antistaphylococcal Conjugate Vaccine"],"prefix":"10.1128","volume":"81","author":[{"given":"Quanyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Dintaman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lees","sequence":"additional","affiliation":[{"name":"Fina BioSolutions, LLC, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goutam","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Solulink, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Shirtliff","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Mond","sequence":"additional","affiliation":[{"name":"BioConsultingSolutions, Columbia, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford M.","family":"Snapper","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/520731"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1211.060190"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16727-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.113.6.1735"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.24.3012"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/19.2.231"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02827.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00438-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(07)70235-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.37.2.215-257.1973"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2009.10.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4049\/jimmunol.113.2.489","article-title":"Characterization of antibodies specific for polyglycerophosphate","volume":"113","author":"Frederick TG","year":"1974","unstructured":"FrederickTGChorpenningFW. 1974. 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