Advancing the development of a Staphylococcus aureus vaccine to prevent postoperative invasive S. aureus disease by targeting multiple bacterial virulence factors

Ingrid L. Scully, Pfizer Vaccine Research; James Baber, Pfizer Vaccine Research; Paul Liberator, Pfizer Vaccine Research; David Cooper, Pfizer Vaccine Research; Edward Zito, Pfizer Vaccine Research; Joseph Eiden, Pfizer Vaccine Research; William Gruber, Pfizer Vaccine Research; Emilio Emini, Pfizer Vaccine Research; Kathrin Jansen, Pfizer Vaccine Research; Alejandra Gurtman, Pfizer Vaccine Research; Annaliesa Anderson, Pfizer Vaccine Research

The Gram positive organism Staphylococcus aureus is responsible for serious postoperative infections, including deep tissue and bloodstream infections.  Risk of infection is dependent on multiple patient factors, including age and comorbidities, as well as numerous procedural factors such as duration and complexity of surgery.   There is currently no licensed vaccine to meet this critical unmet medical need.  

We present a strategy for developing an effective vaccine for the prevention of invasive S. aureus disease by eliciting immune responses targeting important S. aureus virulence factors. 

The vaccine candidate was assessed preclinically using in vivo models of surgical site infection and disseminated disease, and by the development of in vitro immunoassays that measure relevant functional vaccine responses from both preclinical studies and clinical subjects (clinical studies B2251002 (NCT01018641) and B3451001 (NCT01364571)). 

A S. aureus 4-antigen vaccine (SA4Ag), consisting of capsular polysaccharides type 5 and type 8 conjugated to CRM₁₉₇, and recombinant forms of two S. aureus surface proteins, Clumping factor A (ClfA) and Manganese transporter C (MntC) was developed. Selection of the antigens was based on addressing important virulence mechanisms as well as early in vivo expression and efficacy in preclinical animal models. In Phase 1/2 clinical trials, a single administration of an investigational 3-antigen or 4-antigen vaccine exhibited an acceptable safety profile and elicited a functional antibody response in a high proportion of subjects. 

The preclinical and early clinical results support the planned testing of SA4Ag in human efficacy studies.  In addition, the rapid induction of  functional antibodies after a single dose provides a window of opportunity to vaccinate prior to elective surgery.  This represents an important step forward in developing a vaccine to prevent postoperative invasive S. aureus disease.