A randomized phase I study of the safety and immunogenicity of three ascending dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults. Issue 15 (8th April 2015)

• Record Type: Journal Article
• Authors: Nissen, Michael; Marshall, Helen; Richmond, Peter; Shakib, Sepehr; Jiang, Qin; Cooper, David; Rill, Denise; Baber, James; Eiden, Joseph; Gruber, William; Jansen, Kathrin U.; Emini, Emilio A.; Anderson, Annaliesa S.; Zito, Edward T.; Girgenti, Douglas
• Is Part Of: Vaccine. Volume 33:Issue 15(2015)
• Page Start: 1846
• Page End: 1854
• Publication Date: 2015-04-08
• Subjects: Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.02.024
• Languages: English
• ISSNs: 0264-410X

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005"> <italic>Staphylococcus aureus</italic> is a common cause of healthcare-acquired morbidity and mortality and increased healthcare resource utilization. A prophylactic vaccine is being developed that may reduce this disease burden.</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">Volunteers in good general health aged 50–85 (<italic>n</italic> = 312) and 18–24 (<italic>n</italic> = 96) years were randomized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen <italic>S. aureus</italic> vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 and CP8), each conjugated to cross-reactive material 197 (CRM<sub>197</sub>), and recombinant clumping factor A (ClfA). Safety, tolerability, and immunogenicity were evaluated.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">At day 29 post-vaccination, robust immune responses were observed in both age cohorts at all three SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometric mean-fold-rises in competitive Luminex<sup>®</sup> immunoassay antibody titers from baseline ranged from 29.2 to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (<italic>P </italic>< 0.001) exceeding the pre-defined two-fold rise criteria. Similar rises in opsonophagocytic activity assay titers demonstrated functionality of the immune response. Most injection-site reactions were mild in severity and there were no substantial differences (SA3Ag vs. placebo) with regard to systemic or adverse events.</p> </sec> <sec> <title id="sect0025">Conclusions</title> <p id="spar0020">In this study of healthy adults aged 50–85 and 18–24 years, SA3Ag elicited a rapid and robust immune response and was well tolerated, with no notable safety concerns.</p> </sec> </abstract>