The Staphylococcus aureus Cell Wall-Anchored Protein Clumping Factor A Is an Important T Cell Antigen

• DOI: 10.1128/iai.00549-17
• Publication Date: 2017-09-26T00:30:33Z
• Authors: Keenan A. Lacey; John M. Leech; Stephen J. Lalor; Niamh McCormack; Joan A. Geoghegan; Rachel M. McLoughlin
• Keywords: Coagulase; 0301 basic medicine; 570; Antigens, Bacterial; Staphylococcus aureus; 0303 health sciences; T-Lymphocytes; Staphylococcal Vaccines; Staphylococcal Infections; Survival Analysis; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; 616; Microbial Immunity and Vaccines; Animals; Humans; Cells, Cultured

ABSTRACT

Staphylococcus aureus has become increasingly resistant to antibiotics, and vaccines offer a potential solution to this epidemic of antimicrobial resistance. Targeting of specific T cell subsets is now considered crucial for next-generation anti- S. aureus vaccines; however, there is a paucity of information regarding T cell antigens of S. aureus . This study highlights the importance of cell wall-anchored proteins as human CD4 + T cell activators capable of driving antigen-specific Th1 and Th17 cell activation. Clumping factor A (ClfA), which contains N1, N2, and N3 binding domains, was found to be a potent human T cell activator. We further investigated which subdomains of ClfA were involved in T cell activation and found that the full-length ClfA N123 and N23 were potent Th1 and Th17 activators. Interestingly, the N1 subdomain was capable of exclusively activating Th1 cells. Furthermore, when these subdomains were used in a model vaccine, N23 and N1 offered Th1- and Th17-mediated systemic protection in mice upon intraperitoneal challenge. Overall, however, full-length ClfA N123 is required for maximal protection both locally and systemically.