SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies

Vaccine. 2017 Feb 22;35(8):1132-1139. doi: 10.1016/j.vaccine.2017.01.024. Epub 2017 Jan 28.


Background: Staphylococcus aureus is a leading cause of healthcare-associated infections. No preventive vaccine is currently licensed. SA4Ag is an investigational 4-antigen S. aureus vaccine, composed of capsular polysaccharide conjugates of serotypes 5 and 8 (CP5 and CP8), recombinant surface protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (rMntC). This Phase 1 study aimed to confirm the safety and immunogenicity of SA4Ag produced by the final manufacturing process before efficacy study initiation in a surgical population.

Methods: Healthy adults (18-<65years) received one intramuscular SA4Ag injection. Serum functional antibodies were measured at baseline and Day 29 post-vaccination. An opsonophagocytic activity (OPA) assay measured the ability of vaccine-induced antibodies to CP5 and CP8 to kill S. aureus clinical isolates. For MntC and ClfA, antigen-specific immunogenicity was assessed via competitive Luminex® immunoassay (cLIA) and via fibrinogen-binding inhibition (FBI) assay for ClfA only. Reactogenicity and adverse event data were collected.

Results: One hundred participants were vaccinated. SA4Ag was well tolerated, with a satisfactory safety profile. On Day 29, OPA geometric mean titers (GMTs) were 45,738 (CP5, 95% CI: 38,078-54,940) and 42,652 (CP8, 95% CI: 32,792-55,477), consistent with 69.2- and 28.9-fold rises in bacteria-killing antibodies, respectively; cLIA GMTs were 2064.4 (MntC, 95% CI: 1518.2-2807.0) and 3081.4 (ClfA, 95% CI: 2422.2-3920.0), consistent with 19.6- and 12.3-fold rises, respectively. Similar to cLIA results, ClfA FBI titers rose 11.0-fold (GMT: 672.2, 95% CI: 499.8-904.2). The vast majority of participants achieved the pre-defined biologically relevant thresholds: CP5: 100%; CP8: 97.9%, ClfA: 87.8%; and MntC 96.9%.

Conclusions: SA4Ag was safe, well tolerated, and rapidly induced high levels of bacteria-killing antibodies in healthy adults. A Phase 2B efficacy trial in adults (18-85years) undergoing elective spinal fusion is ongoing to assess SA4Ag's ability to prevent postoperative invasive surgical site and bloodstream infections caused by S. aureus. Identifier: NCT02364596.

Keywords: Capsule polysaccharide; Clumping factor A; Functional antibodies; Manganese transporter C; Staphylococcus aureus; Surgical site infection; Vaccine.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Bacterial / blood*
  • Antigens, Bacterial / administration & dosage*
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology
  • Coagulase / administration & dosage
  • Coagulase / biosynthesis
  • Coagulase / genetics
  • Female
  • Healthy Volunteers
  • Humans
  • Immunogenicity, Vaccine
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Patient Safety
  • Periplasmic Binding Proteins / administration & dosage
  • Periplasmic Binding Proteins / biosynthesis
  • Periplasmic Binding Proteins / genetics
  • Polysaccharides, Bacterial / administration & dosage
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / immunology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Serogroup
  • Staphylococcal Infections / prevention & control
  • Staphylococcal Vaccines / administration & dosage*
  • Staphylococcal Vaccines / biosynthesis
  • Staphylococcal Vaccines / genetics
  • Staphylococcus aureus / chemistry
  • Staphylococcus aureus / immunology*
  • Vaccination*
  • Vaccines, Conjugate


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • ClfA protein, Staphylococcus aureus
  • Coagulase
  • Periplasmic Binding Proteins
  • Polysaccharides, Bacterial
  • Recombinant Proteins
  • Staphylococcal Vaccines
  • Vaccines, Conjugate

Associated data