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Updated: May 10, 2025
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Fever exerts opposing effects on the binding affinities of two neutralizing monoclonal antibodies against
Puneet K Singh1, Su-Mi Choi2, Ik Joo Chung3
1Department of Basic Medical Science, Chonnam National University, Hwasun, 58128, Republic of Korea.
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.
Insights
Febrile temperatures differentially impact monoclonal antibodies targeting Staphylococcal Enterotoxin B (SEB). Antibody 14G8 binding affinity increases with fever, while 6D3 activity decreases, suggesting temperature control may optimize therapy.
Area of Science:
- Immunology
- Infectious Diseases
- Biophysics
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections pose significant global health risks.
- Passive immunotherapy using monoclonal antibodies (mAbs) against Staphylococcal Enterotoxin B (SEB) offers a potential treatment strategy.
- Fever is a common symptom during MRSA infections and often coincides with antibody-based therapies.
Purpose of the Study:
- To examine how febrile temperatures influence the immune complex formation between SEB and two therapeutic mAbs, 6D3 and 14G8.
- To understand the temperature-dependent efficacy of SEB-targeting mAbs.
Main Methods:
- Molecular dynamics simulations were employed to model interactions.
- Free binding energy calculations quantified binding strengths.
- Surface Plasmon Resonance (SPR) experiments measured real-time binding kinetics.
Main Results:
- Elevated temperatures (312K/39°C) significantly reduced the activity of the 6D3 mAb.
- Conversely, the binding affinity of the 14G8 mAb was enhanced at febrile temperatures (312K/39°C) compared to physiological temperature (310K/37°C).
Conclusions:
- Febrile conditions have distinct effects on the binding affinities of mAbs targeting SEB.
- Optimizing patient body temperature prior to administering SEB-targeting mAbs could potentially enhance therapeutic outcomes.
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