Staphylococcal protein A (SpA) binds Fcγ and VH3 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 SpAKKAA 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 
SpAKKAA-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.