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Expression and Purification of Virus-like Particles for Vaccination

Expression and Purification of Virus-like Particles for Vaccination

Published on: June 2, 2016

Engineering less immunogenic and antigenic FVIII proteins.

Kathleen P Pratt¹

¹Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.

Cellular Immunology

|November 14, 2015

Summary

Developing less immunogenic blood coagulation factor VIII (FVIII) proteins is key to treating hemophilia A. Strategies focus on modifying epitopes to prevent or overcome dangerous FVIII inhibitors.

Keywords:

Anti-drug antibodies Antigenicity Epitopes Factor VIII Immunogenicity

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Area of Science:

Immunology
Hematology
Biochemistry

Background:

Neutralizing antibodies, or inhibitors, against blood coagulation factor VIII (FVIII) are a major complication in hemophilia A treatment.
These inhibitors impede FVIII's function in the intrinsic tenase complex, crucial for blood coagulation.
While inhibitors affect up to one-third of patients, many develop immune tolerance, suggesting therapeutic potential.

Purpose of the Study:

To explore strategies for designing less immunogenic FVIII proteins to mitigate inhibitor development in hemophilia A.
To investigate methods for modifying FVIII epitopes to improve therapeutic outcomes and induce immune tolerance.

Main Methods:

Identifying and modifying immunodominant T-cell epitopes for FVIII 'de-immunization'.
Altering B-cell epitopes by substituting surface amino acids or attaching moieties to hinder antibody binding.
Employing both experimental and computational approaches to guide protein design.

Main Results:

De-immunization of FVIII by targeting T-cell epitopes aims to reduce immunogenicity.
Modification of B-cell epitopes offers a promising approach for patients with persistent inhibitors.
Combined strategies of less immunogenic proteins and immunotherapies may promote durable immune tolerance.

Conclusions:

Designing less immunogenic FVIII proteins is crucial for advancing hemophilia A therapy.
Targeting both T-cell and B-cell epitopes holds promise for preventing and overcoming FVIII inhibitors.
Future treatments will likely integrate modified proteins with immunotherapies to establish lasting immune tolerance for monogenic diseases.