Impact of oral administration of single strain Lactococcus lactis spp. cremoris on immune responses to keyhole limpet hemocyanin immunization and gut microbiota: A randomized placebo-controlled trial in healthy volunteers

Article

Author: Moerland, Matthijs ; Saghari, Mahdi ; Grievink, Hendrika W ; Gal, Pim ; McHale, Duncan ; Klaassen, Erica S ; Itano, Andrea

IntroductionLactococcus lactis spp. cremoris has been associated with promising immunomodulatory results in preclinical trials. The aim of this study was to investigate the pharmacodynamic (PD) effects of three monoclonal microbial formulations of L. lactis spp. cremoris (EDP1066) on the immune response to keyhole limpet hemocyanin (KLH). Potential effects on the gut microbiota were also investigated.MethodsThe trial was registered on Netherlands Trial Register (trial ID NL7519, https://trialsearch.who.int). Eighty-one healthy subjects (median 28, range 18–59 years) were randomized to 28 days of enteric-coated capsules at five doses (n = 13) (1.5 * 1012 total cells daily), freeze-dried powder at one dose (n = 12) (3.0 * 1011 total cells daily) or five doses (n = 12), minitablets at one dose (n = 12) or five doses (n = 12), or placebo (n = 20) prior to KLH immunization. Antibody responses and circulating regulatory T cells (Tregs) were measured after KLH immunization, and skin responses were evaluated after a KLH rechallenge by laser speckle contrast imaging and multispectral imaging. Ex vivo lymphocyte (phytohemagglutinin) and monocyte (lipopolysaccharide (LPS)) cytokine release assays were explored in the minitablet-treated groups only. The prevalence of L. lactis spp. cremoris in the gastrointestinal tract and the impact on the fecal microbiota were assessed by qPCR and 16S rRNA sequencing, respectively.ResultsRepeated-measures analysis of covariances revealed no significant treatment effects on the antibody responses to KLH, number of Tregs, or KLH skin rechallenge outcomes. Ex vivo LPS-driven cytokine responses in whole blood were lower in the low dose minitablet group compared to placebo: tumor necrosis factor (estimated difference (ED) from placebo: −44.2%, 95% confidence interval (CI) −65.3% to −10.3%), interleukin (IL)-1β (ED −41.4%, 95% CI −63.5% to −5.8%), and IL-6 (ED −39.2%, 95% CI −56.8% to −14.5%). The fecal presence of L. lactis spp. cremoris increased during treatment by all EDP1066 formulations and normalized 5 days after the last dose. Microbiome α-diversity did not change by the treatments compared to placebo.DiscussionThe EDP1066 formulations did not affect the immune response to KLH immunization in healthy individuals. However, exposure to L. lactis spp. cremoris in minitablet formulation impacted ex vivo whole blood LPS cytokine response. The clinical impact of these effects awaits further investigations.Netherlands Trial Registertrialsearch.who.int, trial ID NL7519.

100 Deals associated with EDP-1066

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Colitis, Ulcerative	Phase 1	US	Evelo Biosciences, Inc.	-
Crohn Disease	Phase 1	US	Evelo Biosciences, Inc.	-
Dermatitis, Atopic	Phase 1	GB	-	-
Dermatitis, Atopic	Phase 1	NL	Evelo Biosciences, Inc.	-
Psoriasis	Phase 1	NL	Evelo Biosciences, Inc.	-
Psoriasis	Phase 1	GB	Evelo Biosciences, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

EDP-1066

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation