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Natural Human Immunity Against Staphylococcal Protein A Relies on Effector Functions Triggered by IgG3
Elena Boero1,2, Ana Rita Cruz2, Werner Pansegrau1
1GSK, Siena, Italy.
Frontiers in Immunology
|April 1, 2022
Summary
Staphylococcal protein A (SpA) normally hinders bacterial clearance. However, this study found that IgG3 antibodies targeting SpA can effectively opsonize bacteria, promoting phagocytosis and suggesting a potential protective mechanism against Staphylococcus aureus infections.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Staphylococcal protein A (SpA) is a key virulence factor of Staphylococcus aureus, inhibiting antibody-mediated bacterial clearance by binding IgG.
- SpA's anti-opsonic properties have limited its investigation as a target for promoting phagocytosis.
Purpose of the Study:
- To investigate the presence and function of SpA-opsonizing antibodies in human sera.
- To evaluate the potential of SpA-specific antibodies, particularly IgG3, in mediating phagocytosis of Staphylococcus aureus.
Main Methods:
- Screening of human sera for SpA-opsonizing antibodies.
- Assessing the efficiency of IgG3 Fc in inducing phagocytosis of SpA-expressing S. aureus compared to IgG1 Fc.
- Investigating the influence of antibody epitope recognition on phagocytosis induction.
Main Results:
- Human sera containing IgG3 against SpA were found to effectively opsonize the bacteria.
- IgG3 Fc demonstrated significantly higher efficiency in inducing phagocytosis of SpA-expressing S. aureus compared to IgG1 Fc under physiological conditions.
- The phagocytic capacity induced by SpA antibodies was dependent on the specific epitope recognized on SpA.
Conclusions:
- Anti-SpA IgG3 antibodies can promote the opsonization and phagocytosis of Staphylococcus aureus.
- These findings suggest a potential role for anti-SpA IgG3 in protective immunity against staphylococcal infections.
- Identifying anti-SpA IgG3 as a correlate of protection could guide future therapeutic strategies.
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