Infectious diseaseAdvanced genetic screening to speed vaccine development

Infectious diseases, both old and new, continue to exact a devastating toll, causing some thirteen million fatalities per year around the world.

Vaccines remain the best line of defense against deadly pathogens and now Kathryn Sykes and Stephen Johnston, researchers at Arizona State University’s (ASU) Biodesign Institute, along with co-author Michael McGuire from the University of Texas Southwestern Medical Center, are using clever functional screening methods to attempt to speed new vaccines into production that are both safer and more potent.

In a recent study appearing in the journal Proteome Science, the group used high-throughput methods to identify a modulator of immune activity that exists naturally in an unusual pathogen belonging to the Poxviridae family of viruses.

An Arizona State University release reports that parapoxvirus infection causes immune cell accumulation at the site of infection; direct screening in the host for this biological activity enabled the isolation of an immunomodulator — labeled B2.

Indeed, B2 by itself causes immune cell accumulation at the site of skin injection. When added to a traditional influenza vaccine, B2 improves the vaccine’s protective capacity. Furthermore, the immunomodulator also demonstrated the ability to shrink the size of cancerous tumors, even in the absence of any accompanying specific antigen.

In the past, the process of vaccine discovery involved the random selection of naturally attenuated strains of viruses and bacteria, which were found to provide protection in humans. Examples of this approach include the use of vaccinia to protect against smallpox and attenuated mycobacterium bovis (BCG) to protect against tuberculosis.

In recent years, many vaccines have been developed using only selected portions of a given pathogen to confer immunity. These so-called subunit vaccines have several advantages over whole pathogen vaccines. Genetic components that allow a given pathogen to elude immune detection for example may be screened out, as well as any factors causing unwanted vaccine side effects. Through careful screening, just those elements responsible for eliciting protective immune responses in the host can be extracted from the pathogen and reassembled into an effective, safer subunit vaccine.

In practice, the process of narrowing the field of promising subunit candidates from the whole genome of a pathogen has often been time consuming, laborious and perplexing. In the current study, their earlier-developed strategy, known as expression library immunization, is extended to develop a scheme to find the protein-encoding segments — known as open reading frames (ORFs) — from a pathogenic genome that have any