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Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from<jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>was purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickel-cobalt affinity chromatography was used to prepare highly purified recombinant<jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>Hcp1 and TssM proteins. Immunization of C57BL\/6 mice with CPS-CRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100% of the mice survived a lethal inhalational challenge with<jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>. Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against<jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>as well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.<\/jats:p>","DOI":"10.1128\/iai.00724-17","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T16:20:54Z","timestamp":1509985254000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Development of Subunit Vaccines That Provide High-Level Protection and Sterilizing Immunity against Acute Inhalational Melioidosis"],"prefix":"10.1128","volume":"86","author":[{"given":"Mary N.","family":"Burtnick","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama, USA"},{"name":"Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa L.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama, USA"},{"name":"Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany N.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Muruato","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sbrana","sequence":"additional","affiliation":[{"name":"Department of Pathology, Autopsy Division, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeShazer","sequence":"additional","affiliation":[{"name":"Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo G.","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Brett","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama, USA"},{"name":"Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2015.8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/529290a"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-706X(99)00066-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1385"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.5.890"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/318116"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000900"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/520223"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002877"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyi271"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0912.020750"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1306.060646"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1398389"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0802.010164"},{"key":"e_1_3_3_16_2","first-page":"214","article-title":"Other bacterial diseases as a potential consequence of bioterrorism: Q fever, brucellosis, glanders, and melioidosis","volume":"96","author":"Voskuhl GW","year":"2003","unstructured":"Voskuhl GW, Cornea P, Bronze MS, Greenfield RA. 2003. 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