Safety, tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised, placebo-controlled phase 1/2 study
Robert W Frenck Jr, C Buddy Creech, Eric A Sheldon, David J Seiden, Martin K Kankam, James Baber, Edward Zito, Robin Hubler, Joseph Eiden, Joseph M Severs, Shite Sebastian, Jasdeep Nanra, Kathrin U Jansen, William C Gruber, Annaliesa S Anderson, Douglas Girgenti, Robert W Frenck Jr, C Buddy Creech, Eric A Sheldon, David J Seiden, Martin K Kankam, James Baber, Edward Zito, Robin Hubler, Joseph Eiden, Joseph M Severs, Shite Sebastian, Jasdeep Nanra, Kathrin U Jansen, William C Gruber, Annaliesa S Anderson, Douglas Girgenti
Abstract
Background: A prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag.
Methods: In this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18-64years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo. Functional immune responses were measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding inhibition (FBI) assays; antigen-specific immunogenicity was assessed using a four-plex competitive Luminex® immunoassay (cLIA).
Results: A high proportion of SA4Ag recipients met the pre-defined antibody thresholds for each antigen at Day 29. A substantial and dose-level dependent immune response was observed for rP305A, with up to 18-fold rises in cLIA titres at Day 29. Robust functional responses were demonstrated, with >80-fold and >20-fold rises in OPA assay titres at Day 29 using S. aureus strains expressing capsular polysaccharide serotypes 5 and 8, respectively. Durable antibody responses were observed through month 12, gradually waning from peak levels achieved by days 11-15. SA4Ag was well tolerated, and no vaccine-related serious adverse events were reported.
Conclusions: Single-dose vaccination of SA4Ag in healthy adults aged 18-64years safely induced rapid and robust functional immune responses that were durable through month 12, supporting further development of this vaccine.
Trial registration number: NCT01364571.
Keywords: Capsular polysaccharide; Clumping factor A; Functional antibodies; Manganese transporter C; Staphylococcus aureus; Vaccine.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Source: PubMed