Modified Vaccines for Treatment of Autoimmune and Immunodeficiency Diseases
Recent developments in the treatment of autoimmune and other inflammatory diseases have focused on the use of Intravenous Immunoglobulins (IVIGs). IVIGs are a broad spectrum therapeutic preparation of highly purified polyclonal Immunoglobulin G (IgG) antibodies. They are highly efficacious for eliciting a shift of an immune response from a pro- to anti-inflammatory. But despite their efficacy, the mechanism by which shift is elicited is not understood.
Dr. Jeffrey Ravetch’s laboratory at the Rockefeller University has demonstrated that IgGs’ mediate their inflammatory responses through the Fragment Crystalizable (Fc) fragment (interacts with cell surface receptors and mediates immune response). The composition of sugar groups on the Fc portion is a critical factor in shifting an immune response from pro- to anti-inflammatory. This terminal attachment of the sugar moiety changes the activity of the Fc portion, such that it initiates an inflammatory cascade by binding to lectin receptor (SIGN- RI or DC SIGN), instead of binding with Fc gamma receptors. This leads to upregulation in surface of expression of Fc Receptors on inflammatory cells resulting in attenuation of auto antibody inflammation.
This discovery highlights a broadly applicable technology for designing therapeutic antibodies whose components could be altered for activating an anti-inflammatory pathway in autoimmune or inflammatory disease settings.
Increased protection against autoimmune and other immunodeficiency diseases
Area of Application
Vaccines against multiple diseases – autoimmune and inflammatory
Stage of Development
Discovery in vivo; this variant has been tested in mouse models
Dr. Jeffrey V. Ravetch
- Durandy A.et al, Intravenous Immunoglobulins – understanding problems and mechanisms; Clinical and Experimental Immunology.158 (Sumpl.1):2-13 (2009).
- Anthony R.M. et al, A Novel Role for the IgG Fc Glycan: The Anti-Infammatory Activity of Sialylated IgG Fcs; Journal of Clinical Immunology. 30 (Suppl. 1):S9 – S14 (2010).