title: Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant.
abstract: BACKGROUND
  It has been reported that cytomegalovirus (CMV) pp65-specific T cells can protect hematopoietic cell transplant (HCT) recipients from CMV complications. Two candidate CMV peptide vaccines composed of the HLA A*0201 pp65(495-503) cytotoxic CD8(+) T-cell epitope fused to 2 different universal T-helper epitopes (either the synthetic Pan DR epitope [PADRE] or a natural Tetanus sequence) were clinically evaluated for safety and ability to elicit pp65 T cells in HLA A*0201 healthy volunteers.
  
  
  METHODS
  Escalating doses (0.5, 2.5, 10 mg) of PADRE or Tetanus pp65(495-503) vaccines with (30 adults) or without (28 adults) PF03512676 adjuvant were administered by subcutaneous injection every 3 weeks for a total of 4 injections.
  
  
  RESULTS
  No serious adverse events were reported, although vaccines used in combination with PF03512676 had enhanced reactogenicity. Ex vivo responses were detected by flow cytometry exclusively in volunteers who received the vaccine coadministered with PF03512676. In addition, using a sensitive in vitro stimulation system, vaccine-elicited pp65(495-503) T cells were expanded in 30% of volunteers injected solely with the CMV peptides and in all tested subjects receiving the vaccines coinjected with PF03512676.
  
  
  CONCLUSIONS
  Acceptable safety profiles and vaccine-driven expansion of pp65(495-503) T cells in healthy adults support further evaluation of CMV peptide vaccines combined with PF03512676 in the HCT setting.
  
  
  BACKGROUND
  NCT00722839.
authors.affiliation: Division of Translational Vaccine Research, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
authors.forename: Corinna
authors.initials: C
authors.lastname: La Rosa
authors.forename: Jeff
authors.initials: J
authors.lastname: Longmate
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.forename: Teodora
authors.initials: T
authors.lastname: Kaltcheva
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharan
authors.forename: Denise
authors.initials: D
authors.lastname: Marsano
authors.forename: Peter
authors.initials: P
authors.lastname: Kwon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Drake
authors.forename: Brenda
authors.initials: B
authors.lastname: Williams
authors.forename: Sharon
authors.initials: S
authors.lastname: Denison
authors.forename: Suenell
authors.initials: S
authors.lastname: Broyer
authors.forename: Larry
authors.initials: L
authors.lastname: Couture
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: Sanjeet
authors.initials: S
authors.lastname: Dadwal
authors.forename: Morris I
authors.initials: MI
authors.lastname: Kelsey
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Krieg
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.forename: John A
authors.initials: JA
authors.lastname: Zaia
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014614:Vaccines, Synthetic; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D022482:Cytomegalovirus Vaccines; D000939:Epitopes; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; C401223:PADRE 45; C483020:ProMune; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic