Autologous C5 Vaccines For Treating Complement-Mediated Diseases

Inventors

Feng Lin, PhD
M.G. Finn, PhD

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Jason Ospina, PhD

What is it? What does it do?

The complement system is emerging as a new target for treating many diseases. For example, Eculizumab, a humanized monoclonal antibody against complement component 5 (C5), has been approved for paroxysmal nocturnal hemoglobinuria (PNH) in which patient erythrocytes are lysed by complement. In this study, we developed vaccines to elicit autologous anti-C5 antibody production in mice for complement inhibition. Immunization of mice with a conservative C5 xenoprotein raised high titers of IgG’s against the xenogenous C5, but these antibodies did not reduce C5 activity in the blood. In contrast, an autologous mouse C5 vaccine containing multiple predicted epitopes together with a tolerance-breaking peptide was found to induce anti-C5 autoantibody production in vivo, resulting in decreased hemolytic activity in the blood. We further validated a peptide epitope within this C5 vaccine and created recombinant virus-like particles (VLPs) displaying this epitope fused with the tolerance breaking peptide. Immunizing mice with these novel nanoparticles elicited strong humoral responses against recombinant mouse C5, reduced hemolytic activity, and protected the mice from complement-mediated intravascular hemolysis in a model of PNH. This proof-of-concept study demonstrated that autologous C5-based vaccines could be an effective alternative or supplement for treating complement-mediated diseases such as PNH.
 

Why is it better?

This strategy uses the patient’s own immune system for the long-lasting production of anti-C5 antibodies in vivo, thereby replacing or significantly reducing chronic administration of treatments such as Eculizumab.
 

What is its current status?

Technology has been tested in an animal models of complement-mediated diseases such as Paroxysmal nocturnal hemoglobinuria (PNH). 
 


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