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

Vaccine. 2015 Apr 8;33(15):1846-54. doi: 10.1016/j.vaccine.2015.02.024. Epub 2015 Feb 21.

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.

Trial registration: ClinicalTrials.gov NCT01018641.

Keywords: Capsule proteins; Clinicaltrials.gov Identifier. NCT01018641; Functional antibodies; Staphylococcus aureus; Vaccine.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial / blood*
  • Antigens, Bacterial / immunology
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Vaccines / administration & dosage*
  • Staphylococcal Vaccines / adverse effects
  • Staphylococcal Vaccines / immunology*
  • Staphylococcus aureus / immunology*
  • Vaccination
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Immunoglobulin G
  • Staphylococcal Vaccines

Associated data

  • ClinicalTrials.gov/NCT01018641