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

Elizabeth Begier, David Joshua Seiden, Michael Patton, Edward Zito, Joseph Severs, David Cooper, Joseph Eiden, William C Gruber, Kathrin U Jansen, Annaliesa S Anderson, Alejandra Gurtman

Journal: Vaccine 2017;35(8):1132-1139

PMID: 28143674

Full Text on Elsevier Science View on PubMed

Abstract

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. Clinicaltrials.gov Identifier: NCT02364596.

Address: Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA. Electronic address: [email protected].; Broward Research Group, Hollywood, FL 33024, USA.; Pfizer Vaccine Clinical Research & Development, Maidenhead, UK.; Pfizer, Collegeville, PA, USA(1).; Pfizer Vaccine Clinical Research & Development, Pearl River, NY, USA.; Vaccine Research & Development, Pearl River, NY, USA.

DOI: 10.1016/j.vaccine.2017.01.024

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MeSH Terms: Adolescent, Adult, Aged, Antibodies, Bacterial, Antigens, Bacterial, Coagulase, Female, Healthy Volunteers, Humans, Immunogenicity, Vaccine, Injections, Intramuscular, Male, Middle Aged, Patient Safety, Periplasmic Binding Proteins, Polysaccharides, Bacterial, Recombinant Proteins, Serogroup, Staphylococcal Infections, Staphylococcal Vaccines, Staphylococcus aureus, Vaccination, Vaccines, Conjugate