title: HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood.
abstract: Here, we evaluated innate and adaptive immune system cytokine responses induced by HPV-16 L1 VLP in whole blood (WB) cultures from individuals receiving the vaccine (n=20) or placebo (n=4) before and after vaccination. 11 cytokines were measured: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha, and GM-CSF using multiplex bead arrays. Cytokine profiles from WB samples clearly discriminated between vaccine and placebo recipients and between pre and post-vaccination responses. Significant increases in Th1, Th2 and inflammatory cytokines were observed in WB assays following vaccination. Results from WB assays were compared against parallel PBMC-based assays in a subset of patients. Differences between whole blood assay and PBMC were observed, with the highest levels of induction found for WB for several cytokines. Our results indicate that multiplex assays for cytokine profiling in WB are an efficient tool for assessing broad spectrum, innate and adaptive immune responses to vaccines and identifying immunologic correlates of protection in efficacy studies.
authors.affiliation: SAIC-Frederick, Inc./NCI-Frederick, Room 120, Building 469, Frederick, MD 21702, USA. lpinto@ncifcrf.gov
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Richard B
authors.initials: RB
authors.lastname: Roden
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Harro
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Dora
authors.initials: D
authors.lastname: Wallace
authors.forename: Marcus
authors.initials: M
authors.lastname: Williams
authors.forename: William
authors.initials: W
authors.lastname: Kopp
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D000293:Adolescent; D000328:Adult; D036022:Capsid Proteins / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D027383:Papillomaviridae / Q000254:growth & development / Q000276:immunology*; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology; D053918:Papillomavirus Vaccines; D014412:Tumor Virus Infections / Q000097:blood / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D016207:Cytokines; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines; C063317:L1 protein, Human papillomavirus type 16