title: Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).
abstract: NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24-48 h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity.
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Jacob T
authors: JT
authors: Minang
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Jon R
authors: JR
authors: Inglefield
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Andrea M
authors: AM
authors: Harris
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Janet L
authors: JL
authors: Lathey
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: David G
authors: DG
authors: Alleva
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Diane L
authors: DL
authors: Sweeney
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Robert J
authors: RJ
authors: Hopkins
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA. Electronic address: lacym@ebsi.com.
authors: Michael J
authors: MJ
authors: Lacy
authors: BioDefense Division, Emergent BioSolutions Inc., Gaithersburg, MD 20879, USA.
authors: Edward W
authors: EW
authors: Bernton
mesh_terms: D006801:Humans; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D058501:Enzyme-Linked Immunospot Assay; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D002097:C-Reactive Protein; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; C483020:ProMune
keywords: Anthrax; BioThrax(®); CPG 7909; Cytokine; T cell; Vaccine