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Vaccine. 2017 Jan 5;35(2):375-384. doi: 10.1016/j.vaccine.2016.11.010. Epub 2016 Dec 1.

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.

Author information

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.

KEYWORDS:

Capsular polysaccharide; Clumping factor A; Functional antibodies; Manganese transporter C; Staphylococcus aureus; Vaccine

PMID:
27916408
DOI:
10.1016/j.vaccine.2016.11.010
[Indexed for MEDLINE]
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