Safety, tolerability, and immunogenicity of a single dose 4-antigen or 3-antigen Staphylococcus aureus vaccine in healthy older adults: Results of a randomised trial.

Autor: Creech CB; Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, S-2323 MCN, 1161 21st Avenue South, Nashville, TN 37232, United States. Electronic address: Buddy.creech@vanderbilt.edu., Frenck RW Jr; Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States., Sheldon EA; Miami Research Associates, 6141 Sunset Dr., South Miami, FL 33143, United States., Seiden DJ; Broward Research Group, 7261 Sheridan Street, Suite 210, Hollywood, FL 33024, United States., Kankam MK; Vince and Associates Clinical Research, 10103 Metcalf Ave, Overland Park, KS 66212, United States., Zito ET; Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, United States., Girgenti D; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Severs JM; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Immermann FW; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., McNeil LK; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Cooper D; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Jansen KU; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Gruber W; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Eiden J; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Anderson AS; Pfizer Inc, 401 N Middletown Road, Pearl River, NY 10965, United States., Baber J; Pfizer Australia Pty Ltd, Sydney, 38-42 Wharf Rd, West Ryde, NSW 2114, Australia.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2017 Jan 05; Vol. 35 (2), pp. 385-394. Date of Electronic Publication: 2016 Nov 17.
DOI: 10.1016/j.vaccine.2016.11.032
Abstrakt: Background: The decline in immune function with age is a challenge to vaccine development. Following an initial study in adults aged 18-64years, this study evaluated the safety and immunogenicity of Staphylococcus aureus (S. aureus) 4-antigen (SA4Ag) and 3-antigen (SA3Ag) vaccine in older adults. SA3Ag included capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to the nontoxic mutant form of diphtheria toxin (CRM 197 ) and a recombinant version of clumping factor A (ClfA). SA4Ag included these antigens, with the addition of a recombinant manganese transporter C (rP305A or MntC). Both vaccines were unadjuvanted.
Methods: In this double-blind, sponsor-unblinded, placebo-controlled, phase 1/2 study, 284 healthy adults (aged 65-85years) were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A, SA3Ag, or placebo. Functional immune responses were measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding inhibition (FBI) assays; immunogenicity was also assessed using a competitive Luminex® immunoassay (cLIA). T-cell responses were measured in a small subgroup of subjects using intracellular cytokine staining (ICS) assays.
Results: The results demonstrated rapid and robust functional immune responses to all antigens in healthy older adults. A high proportion of active vaccine recipients met the pre-defined antibody thresholds for each antigen at Day 29. SA4Ag elicited a dose-level response to rP305A with up to a 13-fold rise in cLIA titres at Day 29. Opsonophagocytic activity (OPA) assays showed >50- and >20-fold rises in functional titres using S. aureus strains expressing CP5 and CP8, respectively, at Day 29. T-cell cytokine responses were not substantially above background levels. There were no safety concerns in this study population and no increases in adverse events with higher rP305A dose levels.
Conclusions: Single-dose vaccination of SA4Ag and SA3Ag in healthy adults aged 65-85years safely induced rapid and robust functional immune responses, supporting further development of SA4Ag for the prevention of S. aureus disease in adults up to age 85years.
Trial Registration Number: NCT01643941.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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