Live microbials to boost Anti-SARS-CoV-2 immunity clinical trial (Live BASIC trial): a triple-blind randomized controlled trial
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: PURPOSE: With waning immunity and vaccine hesitancy, the COVID-19 pandemic continues to pose risks. A live microbial consortium (OL-1) with bacteria containing potentially cross-reactive antigens (CRAGs) stimulates anti-SARS-CoV-2 immune responses in vitro/vivo. We evaluated OL-1's efficacy in enhancing anti-SARS-CoV-2 immunity in unvaccinated, previously infected adults. METHODS: We conducted a pilot, parallel-group, triple-blind randomized controlled trial in 2021-2022 involving 52 generally healthy adults ages 18-60, unvaccinated against COVID-19, with SARS-CoV-2 infection ≥ 4 months prior. Participants received 21 days of either standard-dose OL-1, high-dose OL-1, or placebo. The primary outcome was change in plasma anti-SARS-CoV-2 IgG titers from baseline to Day 21. Secondary efficacy outcomes included changes through Day 42, interferon gamma (IFNg) release from stimulated peripheral blood mononuclear cells, and new SARS-CoV-2 infections. Safety was assessed through adverse events. RESULTS: Significant increases in plasma IgG levels were observed by Day 42 in the standard-dose OL-1 group (n = 17) compared to placebo (n = 18) (p = 0.02). No significant changes were observed in the high-dose group (n = 17). Marginal increases in IFNg release were observed in standard-dose recipients after stimulation with CD4+-specific CRAG and SARS-CoV-2 peptides and TLR7 ligands; only changes post-TLR7 ligand stimulation were significant. No new SARS-CoV-2 infections were detected. The most common adverse events overall were mild gastrointestinal symptoms; headaches were more frequent in OL-1 recipients. CONCLUSION: The live microbial consortium OL-1 was well-tolerated and associated with slightly increased anti-SARS-CoV-2 IgG levels in previously infected, unvaccinated adults at standard, but not high, dosage. Further research should confirm these findings and their clinical implications in larger populations. This study was registered on ClinicalTrials.gov (NCT04847349) on April 14, 2021.
Source: Infection
Authors: Daniel B. Horton, Rahul Ukey, Abhilasha Madhvi, Tracy Andrews, Veenat Parmar, Nancy Reilly, Sanna M. Mäkelä, Jonathan Peterson, Leah Hustad, Gloriana Wong, Emily S. Barrett, Natalie Bruiners, Jeffrey L. Carson, Kylie Getz, Patricia Greenberg, Alicia Iizuka, Jason Roy, Alexander W. Pastuszak, Markus J. Lehtinen, Martin J. Blaser, Reynold A. Panettieri, Maria Laura Gennaro
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funders: National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Cohort and biomarkers for COVID-19 severity, natural history, and reinfection, G1767170664, COVID-19 Network of Networks Expanding Clinical and Translational approaches to Predict Severe Illness in Children (CONNECT to Predict SIck Children), G3307304245, G3797236039, G5631216655, COVID-19 Network of Networks Expanding Clinical and Translational approaches to Predict Severe Illness in Children (CONNECT to Predict SIck Children), G8877806054, G979940031
OpenAlex ID: W4416716335