Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers

Melissa Dsouza; Rajita Menon; Emily Crossette; Shakti K Bhattarai; Jessica Schneider; Yun-Gi Kim; Shilpa Reddy; Silvia Caballero; Cintia Felix; Louis Cornacchione; Jared Hendrickson; Andrea R Watson; Samuel S Minot; Nick Greenfield; Lisa Schopf; Rose Szabady; Juan Patarroyo; William Smith; Pratibha Harrison; Ed J Kuijper; Ciaran P Kelly; Bernat Olle; Dmitri Bobilev; Jeffrey L Silber; Vanni Bucci; Bruce Roberts; Jeremiah Faith; Jason M Norman

doi:10.1016/j.chom.2022.03.016

Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers

Cell Host Microbe. 2022 Apr 13;30(4):583-598.e8. doi: 10.1016/j.chom.2022.03.016.

Authors

Melissa Dsouza¹, Rajita Menon¹, Emily Crossette¹, Shakti K Bhattarai², Jessica Schneider¹, Yun-Gi Kim¹, Shilpa Reddy¹, Silvia Caballero¹, Cintia Felix¹, Louis Cornacchione¹, Jared Hendrickson¹, Andrea R Watson¹, Samuel S Minot³, Nick Greenfield⁴, Lisa Schopf¹, Rose Szabady¹, Juan Patarroyo¹, William Smith¹, Pratibha Harrison⁵, Ed J Kuijper⁶, Ciaran P Kelly⁷, Bernat Olle¹, Dmitri Bobilev¹, Jeffrey L Silber¹, Vanni Bucci², Bruce Roberts¹, Jeremiah Faith⁸, Jason M Norman⁹

Affiliations

¹ Vedanta Biosciences, Inc., Cambridge, MA 02139, USA.
² University of Massachusetts Medical School, Department of Microbiology and Physiological Systems, Worcester, MA 01605, USA.
³ Microbiome Research Initiative, Fred Hutchison Cancer Research Center, Seattle, WA, USA.
⁴ One Codex, Invitae, San Francisco, CA 94103, USA.
⁵ University of Massachusetts Dartmouth, Bioengineering and Research Core for Microbial Informatics, Dartmouth, MA 02747, USA.
⁶ Leiden University Medical Center, Leiden, the Netherlands.
⁷ Beth Israel Deaconess Center, Boston, MA 02215, USA.
⁸ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁹ Vedanta Biosciences, Inc., Cambridge, MA 02139, USA. Electronic address: jnorman@vedantabio.com.

PMID: 35421353
DOI: 10.1016/j.chom.2022.03.016

Abstract

Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.

Keywords: C. difficile infection; antibiotics; live biotherapeutic product; metabolites; metagenomics; microbiome; pharmacology.

MeSH terms

Clostridioides difficile*
Clostridium Infections* / microbiology
Clostridium Infections* / therapy
Fecal Microbiota Transplantation / methods
Healthy Volunteers
Humans
Microbiota*