Peptide libraries for viral diseases

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Overview

Improving diagnostics and treatments for infectious diseases with peptide libraries

In general, for animal viruses to replicate they must penetrate the host cell to hijack the host replication machinery. For this to occur, the virus first recognizes and binds to specific receptors on the cell surface, resulting in fusion of the viral envelope with the cell membrane and subsequent endocytosis. At this point an immune response can be stimulated when the infected cell displays viral particles via MHC I receptors. Upon recognition by a CTL, the infected cell can then be destroyed, or antibodies can be synthesized against the virus for subsequent agglutination. While the immune system can successfully eliminate viral infections in this manner, there are many viruses that escape the immune system altogether. Peptide libraries, which are comprised of systematic combinations of antigenic peptide fragments, can accelerate the discovery and design of vaccines for these types of viral diseases.

Discovery of mimotopes using peptide libraries

Mimotopes, or peptides that mimic an epitope, are commonly used to develop vaccines and antibodies against multiple types of viral diseases. Because of the structural similarity, these peptides will stimulate an immune response and be recognized by the same antibodies. Peptide libraries are almost exclusively used to find these mimotopes, since they drastically reduce the amount of time needed for screening. Once the epitopes have been identified, they can be used to develop serodiagnostics or identify antibodies that might be used for vaccine development. Recent studies have applied this research to epitope discovery for Lyme Disease, Hepatitis C, and West Nile Virus among others.

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Improving vaccine efficiency by targeting specific viral epitopes

Unlike attenuated or killed vaccines, subunit vaccines are often more effective vaccine alternatives that can be produced at lower cost. These subunits are comprised of single or multi-epitope peptides that can increase immunity against the specific virus following vaccination. A complication to this approach is that these peptide sequences need to first be identified, which can be challenging with viruses that undergo antigenic changes as a result of antigenic shift or drift, such as the influenza virus or HIV.

To simplify the vaccine design process, epitope discovery is utilized to span the entire sequences of known viral protein antigens. These peptide sequences are used to predict the B- and T-cell epitopes to stimulate passive immunity. Examples of studies that have used peptide libraries for vaccine development against viral diseases are:

Severe Acute Respiratory Syndrome (SARS): peptide libraries were used to screen for B-cell epitopes that recognize the SARS virus for developing a diagnostic tool

Herpes simplex virus: libraries containing sequences of a specific glycoprotein on Herpes simplex was screened with monoclonal antibodies to find the peptide with the highest binding affinity

Japanese encephalitis virus (JEV): the envelope protein of JEV was screened to identify functional epitopes that can be targeted with neutralizing antibodies