Understanding, Leveraging & Engineering the Human Virome

The human virome is the total collection of viruses in and on the human body. Viruses in the human body may infect both human cells and other microbes such as bacteria (as with bacteriophages). This session will look at understanding these viral communities, the potential for leveraging viruses to treat disease, regulatory and manufacturing challenges as well as synthetically programming bacteriophages.

The Virome and its Potential for Shaping the Microbiome

By David T Pride, Associate Adjunct Professor at University of California San Diego

Viruses are the most abundant members of the human microbiome, yet relatively little is known about their ecology or their role in this diverse ecosystem. Because the majority of the identifiable viruses in the microbiome are bacteriophages, they could have substantial impacts upon the ecology of their host bacterial communities. A substantial proportion of the bacteriophages in the human microbiome are highly persistent, which suggests that they have evolved a dynamic equilibrium with their cellular hosts. We have been working to uncover the ecology of viral communities on human body surfaces to understand whether their ecology provides clues into the interactions between bacteria and their viruses in the human body. We have identified separate ecological groups that are distinguishable by alpha diversity, beta diversity, taxonomy, and virus sharing across body surfaces. Those surfaces inhabited by diverse bacterial communities also have diverse viral communities. In contrast, surfaces inhabited by few if any bacteria have low diversity viral communities. To decipher the role of phages in these communities, we have been developing chemostat culture systems that simulate the magnitude, diversity, and taxonomy of bacteria and their viruses in the distal colon. There is dysbiosis in bacterial communities in a number of human disease conditions. We plan to use these cultured microbial ecosystems to assess the role of phages as potential drivers of bacterial dysbiosis in human microbial communities.

Dr. Pride is originally from Nashville, Tennessee. He received his undergraduate degree in biology from Wake Forest University, his Ph.D. in Microbiology and Immunology from Vanderbilt University, and his M.D. at New York University. He is board certified in Internal Medicine, and received subspecialty training in Infectious Diseases at Stanford University. Dr. Pride serves as the Director of the Molecular Microbiology laboratory and the Associate Director of the Clinical Microbiology laboratory at UC San Diego Health. Dr. Pride’s major interests are in developing diagnostic tests for infectious diseases, and in understanding the role of microbial communities in health and disease.

Regulatory and Manufacturing Compliance of Phage Therapy Products

By Laurent Bretaudeau, Director at LB4Biotech Consulting

Facing the emergence of difficult-to-treat bacterial infections, the perspective of using the anti-bacterial potential of bacteriophages has re-gained a significant interest in many countries. In Western countries , bacteriophages are not of common use, and, in turns, do not have a specific regulatory framework, for both the use and the production of the phages. From a pharmaceutical classification point of view, phages fall in the categories of anti-infectious products and of biological products, given the intended use and their live nature. In addition, the compliance to the Good Manufacture Practices (GMP) is a requirement for any medicinal product. During the EU-funded PhagoBurn’s project, we solved the challenges of 1) producing two cocktails of lytic bacteriophages in compliance with the GMPs, 2) performing a phase I-II clinical trial on burn patients suffering from E. coli or P. aeruginosa infections. The rich interactions with the national authorities in 3 countries (France, Belgium, and Switzerland) during PhagoBurn’s experience, and in other phage-therapy projects, have shown the interest of the authorities to investigate the potential of phage therapy. Accordingly, the working frame for new development is better determined.

As head of R&D for Clean Cells, Laurent Bretaudeau contributed to the growth of the company by implementing innovative quality control methods and developing the manufacturing of biological products under Good Manufacturing Production (GMP) compliance. He supervised the GMP production of bacteriophages for the phage therapy program PhagoBurn. During this European project, bacteriophages were used in a clinical trial with infected burn patients. Laurent had a major contribution in the regulatory process through the communication with the health authorities during the PhagoBurn project, and now in other projects based on phage therapy.

Using Synthetic Engineering to Develop Novel Phage Therapies for Chronic Diseases

By Assaf Oron, Chief Business Officer, BiomX

BiomX is a microbiome drug discovery company developing customized phage therapies that seek and destroy harmful bacteria in chronic diseases such as IBD, liver disease and cancer. We discover and validate proprietary bacterial targets and customize our natural and engineered phage compositions against these targets. In this talk we will provide demonstration of the synthetic biology we use to ‘reprogram’ phages in order to optimize their performance for therapeutic applications. Synthetic biology used includes “reprogramming” of lysogenic (dormant) phage to a strictly lytic (active) mode, and the expansion of the phage host range to both achieve eradication of a wider array of bacterial strains and overcome bacterial resistance.

Assaf Oron has served as Chief Business Officer since January 2017. Prior to this position, he served for over a decade at Evogene (NYSE:EVGN), an agriculture biotechnology company which utilizes a proprietary integrated technology infrastructure to enhance seed traits underlying crop productivity. At Evogene, he worked in various roles such as executive vice president of corporate development and executive vice president of strategy and business development. Mr. Oron holds an M.Sc. in Biology (bioinformatics) and a B.Sc. in Chemistry and Economics, both from Tel Aviv University.

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