Microbiome-Derived Therapies for Treatment and Prevention Viral Infections

Background & Unmet Need

• There are few antivirals for many viral infections including SARS-CoV-2, influenza, Zika, and CMV
• Limited access to antiretroviral therapy (ART) underlies most new HIV infections and HIV-related deaths
• Barriers to ART and other antivirals include toxicity, side effects, financial constraints, and lack of access to medical care
• There are few broad-spectrum antivirals, which would have the capacity to treat several different viruses
• Unmet Need: Development of novel antiviral strategies to overcome the lack of effective treatments, toxicity of current ARTs, and barriers to medicine for viral infections

Technology Overview

• The Technology: Methods of preventing viral infection, including HIV or CMV, using an aryl hydrocarbon receptor (AhR) agonist or Lachnospriaceae family bacteria
• The Discovery: Lachnospriaceae family members Clostridium immunis (C. immunis) and Ruminococcus gnavus (R. gnavus) metabolize tryptophan into 3-indolelactic acid (3-ILA) via Aromatic Amino Acid Aminotransferase (ArAT)
• 3-ILA and FICZ (an alternative agonist) can prevent HIV infection by binding to aryl hydrocarbon receptor (AhR)
• PoC Data: Administration of C. immunis as a live biotherapeutic suppresses active HIV replication by up to 80-90% in vitro in an ArAT dependent manner
• Administration of FICZ suppresses active HIV replication by up to 50% in vitro

Technology Applications

• Use of small molecule AhR agonists or Lachnospriaceae live biotherapeutics to prevent HIV infection in infants who breast-feed from HIV-positive mothers
• Prevention or treatment of other viral infections including HIV, CMV, and potentially SARS-CoV-2, influenza, Hepatitis C, and Zika

Technology Advantages

• AhR agonists or Lachnospriaceae bacteria are broad-spectrum and can be used for co-infections
• Prolonged colonization of Lachnospriaceae in patients can prevent the need for re-dosing
• AhR agonists or Lachnospriaceae can be used as a monotherapy, rather than in combination like ARTs
• May overcome the toxicity of current ART regimens

Figure 1: Schematic of HIV inhibition by C. immunis. C. immunis preventsHIV infection by expressing ArAT, which produces, 3-ILA, which activates Ahr.