A monoclonal antibody that recognizes the E domain of staphylococcal protein A

作者：Kim Hwan Keun; Emolo Carla; Missiakas Dominique; Schneewind Olaf^*

来源：Vaccine, 2014, 32(4): 464-469.

DOI：10.1016/j.vaccine.2013.11.054

• Staphylococcal protein A
• B Cell superantigen
• Opsonophagocytic clearance
• Therapeutic vaccine
• Disease protection
• Monoclonal antibody

Staphylococcal protein A (SpA) binds Fc gamma and V(H)3 clan Fab domains of human and animal immunoglobulin (Ig) with each of its five Ig binding domains (IgBDs), thereby supporting Staphylococcus aureus escape from opsonophagocytic killing and suppressing adaptive B cell responses. The variant SpA(KKAA) cannot bind Ig yet retains antigenic properties that elicit SpA-neutralizing antibodies and disease protection in mice, whereas S. aureus infection or SpA-immunization cannot elicit neutralizing antibodies. As a test for this model, we analyzed here mAb 358A76, which was isolated from SpA-immunized mice. Unlike SpA(KKAA)-derived mAbs, mAb 358A76 binds only the first IgBD (E) but not any of the other four IgBDs (D-A-B-C) and its binding can neutralize only the E domain of SpA, which does not provide disease protection in mice. These results are in agreement with a model whereby wild-type SpA-immunization generates a limited antibody response without neutralizing and/or disease protective attributes.

• 出版日期2014-1-16