title: A randomized phase I study of the safety and immunogenicity of three ascending dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults.
abstract: BACKGROUND
  Staphylococcus aureus is a common cause of healthcare-acquired morbidity and mortality and increased healthcare resource utilization. A prophylactic vaccine is being developed that may reduce this disease burden.
  
  
  METHODS
  Volunteers in good general health aged 50-85 (n=312) and 18-24 (n=96) years were randomized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen S. aureus vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 and CP8), each conjugated to cross-reactive material 197 (CRM197), and recombinant clumping factor A (ClfA). Safety, tolerability, and immunogenicity were evaluated.
  
  
  RESULTS
  At day 29 post-vaccination, robust immune responses were observed in both age cohorts at all three SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometric mean-fold-rises in competitive Luminex(®) immunoassay antibody titers from baseline ranged from 29.2 to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (P<0.001) exceeding the pre-defined two-fold rise criteria. Similar rises in opsonophagocytic activity assay titers demonstrated functionality of the immune response. Most injection-site reactions were mild in severity and there were no substantial differences (SA3Ag vs. placebo) with regard to systemic or adverse events.
  
  
  CONCLUSIONS
  In this study of healthy adults aged 50-85 and 18-24 years, SA3Ag elicited a rapid and robust immune response and was well tolerated, with no notable safety concerns.
authors.affiliation: Queensland Paediatric Infectious Diseases Clinical Trials Centre, Royal Children's Hospital and Children's Health Queensland, Brisbane, QLD, Australia. Electronic address: theniss@uq.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Nissen
authors.affiliation: Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital and Robinson Research Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia. Electronic address: helen.marshall@adelaide.edu.au.
authors.forename: Helen
authors.initials: H
authors.lastname: Marshall
authors.affiliation: University of Western Australia School of Paediatrics and Child Health & Telethon Kids Institute, Perth, WA, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Richmond
authors.affiliation: CMAX, Adelaide, SA, Australia.
authors.forename: Sepehr
authors.initials: S
authors.lastname: Shakib
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Pfizer Inc., Pearl River, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Rill
authors.affiliation: Pfizer Australia Pty Ltd, Sydney, NSW, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Baber
authors.affiliation: Pfizer Inc., Pearl River, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Eiden
authors.affiliation: Pfizer Inc., Pearl River, NY, USA.
authors.forename: William
authors.initials: W
authors.lastname: Gruber
authors.affiliation: Pfizer Inc., Pearl River, NY, USA.
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.affiliation: Pfizer Inc., Pearl River, NY, USA.
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Zito
authors.affiliation: Pfizer Inc., Pearl River, NY, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Girgenti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D013209:Staphylococcal Vaccines
keywords: Capsule proteins; Clinicaltrials.gov Identifier. NCT01018641; Functional antibodies; Staphylococcus aureus; Vaccine