Robert W Frenck1, C Buddy Creech2, Eric A Sheldon3, David J Seiden4, Martin K Kankam5, James Baber6, Edward Zito7, Robin Hubler7, Joseph Eiden8, Joseph M Severs8, Shite Sebastian8, Jasdeep Nanra8, Kathrin U Jansen8, William C Gruber8, Annaliesa S Anderson8, Douglas Girgenti8. 1. Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States. Electronic address: robert.frenck@cchmc.org. 2. Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, S-2323 MCN, 1161 21st Avenue South, Nashville, TN 37232, United States. 3. Miami Research Associates, 6141 Sunset Dr., South Miami, FL 33143, United States. 4. Broward Research Group, 7261 Sheridan Street, Suite 210, Hollywood, FL 33024, United States. 5. Vince and Associates Clinical Research, 10103 Metcalf Ave, Overland Park, KS 66212, United States. 6. Pfizer Australia Pty Ltd, Sydney, 38-42 Wharf Rd, West Ryde, NSW 2114, Australia. 7. Pfizer Vaccine Research and Development, Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, United States. 8. Pfizer Vaccine Research and Development, Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States.
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.
RCT Entities:
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.
Authors: Janette M Harro; Yvonne Achermann; Jeffrey A Freiberg; Devon L Allison; Kristen J Brao; Dimitrius P Marinos; Salar Sanjari; Jeff G Leid; Mark E Shirtliff Journal: Infect Immun Date: 2019-12-17 Impact factor: 3.441
Authors: Fermin E Guerra; Timothy R Borgogna; Delisha M Patel; Eli W Sward; Jovanka M Voyich Journal: Front Cell Infect Microbiol Date: 2017-06-30 Impact factor: 5.293
Authors: Fleur P Paling; Karina Olsen; Kristin Ohneberg; Martin Wolkewitz; Vance G Fowler; Mark J DiNubile; Hasan S Jafri; Frangiscos Sifakis; Marc J M Bonten; Stephan J Harbarth; Jan A J W Kluytmans Journal: PLoS One Date: 2018-03-21 Impact factor: 3.240