http://orcid.org/0000-0001-6798-4399
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ABSTRACT
A novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, tolerability, and immunogenicity in Japanese adults aged 20 to 64 and 65 to 85 years.
A total of 136 healthy Japanese adults (68 per age group) were randomized 1:1 to receive single-dose SA4Ag or placebo intramuscularly (Day 1). Safety assessments included reactogenicity and adverse events. The ability of the vaccine to induce immune responses that are considered functional due to their ability to facilitate the killing of S. aureus or neutralize S. aureus virulence mechanisms was assessed using 5 different antigen-specific assays.
SA4Ag was well tolerated in both age groups, with no safety concerns. At Day 29, > 85% of SA4Ag recipients in each age group achieved predefined thresholds for each antigen. Antibody geometric mean-fold rises from baseline to Day 29 in SA4Ag groups were: > 80 and > 30 for CP5 and CP8 (opsonophagocytic activity assay), > 10 for ClfA (fibrinogen-binding inhibition assay), and > 15 and > 7 for ClfA and MntC (competitive Luminex® immunoassay), respectively. Antibody titers decreased through Month 12 but remained well above baseline and placebo levels.
SA4Ag had an acceptable safety profile and induced rapid and robust functional immune responses in both age groups. These results support ongoing development of SA4Ag for the prevention of invasive S. aureus disease in elective-surgery patients in Japan, North America, and Europe.
Abbreviations
| AE | = | Adverse event |
| CI | = | Confidence interval |
| ClfA | = | Clumping factor A |
| cLIA | = | Competitive Luminex® immunoassay |
| CP5 | = | Capsular polysaccharide serotype 5 |
| CP8 | = | Capsular polysaccharide serotype 8 |
| CRM197 | = | Cross-reactive material 197 |
| FBI | = | Fibrinogen-binding inhibition |
| GCP | = | Good Clinical Practice |
| GMFR | = | Geometric mean-fold rise |
| GMT | = | Geometric mean titer |
| HBV | = | Hepatitis B virus |
| HCV | = | Hepatitis C virus |
| HIV | = | Human immunodeficiency virus |
| ICH | = | International Council for Harmonisation |
| LLOQ | = | Lower limit of quantitation |
| MedDRA | = | Medical Dictionary for Regulatory Activities |
| mITT | = | Modified intention-to-treat |
| MntC | = | Manganese transporter protein C |
| MRSA | = | Methicillin-resistant Staphylococcus aureus |
| OPA | = | Opsonophagocytic activity |
| rmClfA | = | Recombinant protein clumping factor A |
| rP305A | = | Recombinant protein 305A |
| SA3Ag | = | Staphylococcus aureus 3-antigen |
| SA4Ag | = | Staphylococcus aureus 4-antigen |
| SAE | = | Serious adverse event |
| SSI | = | Surgical-site infection |
| US | = | United States |
Acknowledgments
Editorial support was provided by Shuang Li, PhD, and Chu Kong Liew, PhD, of Engage Scientific Solutions.
Disclosure statement
James Baber, Yasuko Shoji, Masakazu Aizawa, David Cooper, William C. Gruber, Kathrin U. Jansen, Annaliesa S. Anderson, and Alejandra Gurtman are employees of Pfizer. Joseph Eiden was an employee of Pfizer when the study was being conducted. Megumi Inoue and Takuma Yonemura have no conflicts of interest to declare.