Safety, Tolerability and Immunogenicity of a Single Dose 4-antigen or 3-antigen Staphylococcus aureus Vaccine in Healthy Older Adults

Background: We evaluated the safety, tolerability and immunogenicity of a single-dose Staphylococcus aureus vaccine (4-antigen [SA4Ag] or 3-antigen [SA3Ag]) in adults aged 65-85 years, following a similar study in a younger population (18-64 years). SA4Ag and SA3Ag contain capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM₁₉₇, and recombinant surface protein clumping factor A (rmClfA). SA4Ag also contains recombinant manganese transporter protein C (rP305A).

Methods: Healthy adults (283) were vaccinated with an IM injection of 1 of the 3 SA4Ag formulations, SA3Ag, or placebo. Both SA4Ag and SA3Ag have fixed doses of 30 µg CP5-CRM₁₉₇ /30 µg CP8-CRM₁₉₇/60 µg of rmClfA. SA4Ag also includes low- [20 µg], mid- [60 µg], or high- [200 µg] dose rP305A). Reactogenicity and adverse event data were collected. Functional immunogenicity was evaluated with opsonophagocytic activity (OPA) killing assays using CP5- and CP8-expressing clinical S. aureus strains and a fibrinogen binding inhibition (FBI) assay to measure ClfA responses. A competitive Luminex^® immunoassay (cLIA) assessed antigen-specific competitive-binding antibody response to each of the 4 antigens in SA4Ag using predefined thresholds.

Results: Vaccines were well tolerated with an acceptable safety profile. At Day 29 postvaccination, 100% of SA4Ag and 97.8% of SA3Ag recipients achieved the CP5 OPA threshold compared with placebo (5.2%); 87.5-92.6% of SA4Ag and 97.7% of SA3Ag recipients achieved the CP8 OPA threshold compared with placebo (19.3%). A robust functional response was observed for rmClfA with ≥4-fold rise in FBI titers in 70.2-84.2% of SA4Ag and 80.4% of SA3Ag recipients compared with placebo (0%). A dose-response was observed for rP305A with 43.1% (low-dose), 56.1% (mid-dose), and 66.7% (high-dose) rP305A recipients achieving the cLIA threshold compared with placebo (1.7%). Substantial increases in cLIA geometric mean titers (GMTs) for all antigens were evident by Day 8, with peak responses generally noted around Day 15. GMTs gradually decreased through Month 12 but remained well above baseline.

Conclusion:  SA4Ag and SA3Ag were safe, well tolerated and induced rapid rises in functional antibody responses in healthy older adults. The data support ongoing development of SA4Ag for the prevention of invasive S. aureus disease in patients undergoing elective surgery.