Performance of a Four-Antigen Staphylococcus aureus Vaccine in Preclinical Models of Invasive S. aureus Disease

Ingrid L Scully; Yekaterina Timofeyeva; Arthur Illenberger; Peimin Lu; Paul A Liberator; Kathrin U Jansen; Annaliesa S Anderson

doi:10.3390/microorganisms9010177

Performance of a Four-Antigen Staphylococcus aureus Vaccine in Preclinical Models of Invasive S. aureus Disease

Microorganisms. 2021 Jan 15;9(1):177. doi: 10.3390/microorganisms9010177.

Authors

Ingrid L Scully¹, Yekaterina Timofeyeva¹, Arthur Illenberger¹, Peimin Lu¹, Paul A Liberator¹, Kathrin U Jansen¹, Annaliesa S Anderson¹

Affiliation

¹ Pfizer Vaccine Research & Development, Pearl River, NY 10965, USA.

Abstract

A Staphylococcus aureus four-antigen vaccine (SA4Ag) was designed for the prevention of invasive disease in surgical patients. The vaccine is composed of capsular polysaccharide type 5 and type 8 CRM₁₉₇ conjugates, a clumping factor A mutant (Y338A-ClfA) and manganese transporter subunit C (MntC). S. aureus pathogenicity is characterized by an ability to rapidly adapt to the host environment during infection, which can progress from a local infection to sepsis and invasion of distant organs. To test the protective capacity of the SA4Ag vaccine against progressive disease stages of an invasive S. aureus infection, a deep tissue infection mouse model, a bacteremia mouse model, a pyelonephritis model, and a rat model of infectious endocarditis were utilized. SA4Ag vaccination significantly reduced the bacterial burden in deep tissue infection, in bacteremia, and in the pyelonephritis model. Complete prevention of infection was demonstrated in a clinically relevant endocarditis model. Unfortunately, these positive preclinical findings with SA4Ag did not prove the clinical utility of SA4Ag in the prevention of surgery-associated invasive S. aureus infection.

Keywords: ClfA; MntC; SA4Ag vaccine; Staphylococcus aureus; animal models; conjugated polysaccharide; invasive disease; protection; sepsis; surgery-associated infection.