Fever exerts opposing effects on the binding affinities of two neutralizing monoclonal antibodies against Staphylococcal Enterotoxin B

Rationale

Infections with methicillin-resistant Staphylococcus aureus are a major source of morbidity and mortality worldwide. While no vaccines against this pathogen are yet available, passive therapy with neutralizing monoclonal antibodies against a key S. aureus toxin, the Staphylococcal Enterotoxin B (SEB), can be clinically effective. Further, fever response is a key symptom of this infection, and typically precedes or is concomitant to antibody therapy against SEB.

Objective

To investigate the role of febrile temperatures on the formation of immune complexes between SEB and two therapeutic monoclonal antibodies, 6D3 and 14G8.

Results

Using molecular dynamics simulations, free binding energy calculations and Surface Plasmon Resonance experiments, we reveal that at high fever (i.e. 312K (39 °C), compared to the physiologic body temperature of 310K (37 °C), the activity of 6D3 mAb is markedly reduced. In contrast, the binding affinity of antibody 14G8 benefits from the higher temperature.

Conclusions

Febrile temperatures differentially affect the binding affinities of monoclonal antibodies used in the therapy against S. aureus, and judicious control of the body temperature of the patients before their administration may potentiate their activity.