title: A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.
abstract: BACKGROUND
  Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.
  
  
  METHODS
  The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted.
  
  
  RESULTS
  There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+T-cell responses to IE1; 3 responded to 1-2 additional antigens.
  
  
  CONCLUSIONS
  The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate.
  
  
  BACKGROUND
  NCT01195571.
authors: CMV Research Foundation.
authors: Stuart P
authors: SP
authors: Adler
authors: CMV Research Foundation.
authors: Anne-Marie
authors: AM
authors: Manganello
authors: Department of Pediatrics.
authors: Ronzo
authors: R
authors: Lee
authors: Department of Pediatrics.
authors: Michael A
authors: MA
authors: McVoy
authors: Department of Internal Medicine, Virginia Commonwealth University, Richmond.
authors: Daniel E
authors: DE
authors: Nixon
authors: University of Pennsylvania.|Wistar Institute, Philadelphia, Pennsylvania.
authors: Stanley
authors: S
authors: Plotkin
authors: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, Georgia.
authors: Edward
authors: E
authors: Mocarski
authors: International AIDS Vaccine Initiative, New York.
authors: Josephine H
authors: JH
authors: Cox
authors: International AIDS Vaccine Initiative, New York.
authors: Patricia E
authors: PE
authors: Fast
authors: Department of Molecular Microbiology and Immunology, Oregon Health and Science University.
authors: Pavlo A
authors: PA
authors: Nesterenko
authors: Department of Molecular Microbiology and Immunology, Oregon Health and Science University.|Department of Biology, University of Portland, Oregon.
authors: Susan E
authors: SE
authors: Murray
authors: Department of Molecular Microbiology and Immunology, Oregon Health and Science University.
authors: Ann B
authors: AB
authors: Hill
authors: 3-V Biosciences, Menlo Park, California.
authors: George
authors: G
authors: Kemble
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: cytomegalovirus; pregnancy; transplantation; vaccines