title: SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies.
abstract: 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.
  
  
  
  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.
  
  
  
  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%.
  
  
  
  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. Clinicaltrials.gov Identifier: NCT02364596.
authors.affiliation: Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA. Electronic address: elizabeth.begier@pfizer.com.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Begier
authors.affiliation: Broward Research Group, Hollywood, FL 33024, USA.
authors.forename: David Joshua
authors.initials: DJ
authors.lastname: Seiden
authors.affiliation: Pfizer Vaccine Clinical Research & Development, Maidenhead, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Patton
authors.affiliation: Pfizer, Collegeville, PA, USA(1).
authors.forename: Edward
authors.initials: E
authors.lastname: Zito
authors.affiliation: Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Severs
authors.affiliation: Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.affiliation: Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Eiden
authors.affiliation: Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Gruber
authors.affiliation: Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.affiliation: Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
authors.affiliation: Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gurtman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D003030:Coagulase / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D033902:Periplasmic Binding Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D065288:Serogroup; D013203:Staphylococcal Infections / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D033902:Periplasmic Binding Proteins; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D013209:Staphylococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Capsule polysaccharide; Clumping factor A; Functional antibodies; Manganese transporter C; Staphylococcus aureus; Surgical site infection; Vaccine