IMM-201 / Immodulon - LARVOL DELTA

Immunity Against Mycobacterium avium Induced by DAR-901 and BCG. (PubMed, Vaccines (Basel)) - " Our results showed that (i) DAR-901 induced cross-reactive immunity to MAC to a similar level as BCG, (ii) DAR-901 and BCG protected against aerosol MAC challenge, (iii) mucosal BCG vaccination, compared to systemic BCG and DAR-901 vaccinations, provided the best protection against MAC challenge, (iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin, (v) BCG-vaccinated mice had increased inflammation and increased frequencies of activated CD4 and CD8 T cells following MAC infection, and (vi) doxycycline treatment of tetR BCG-vaccinated mice decreased lung BCG CFU without affecting MAC immunity. Both DAR-901 and BCG vaccinations induce MAC cross-reactive immunity and protect against aerosolized MAC challenges. Mucosal BCG vaccination provides the best protection and TetR BCG could enhance the safety of mucosal BCG vaccination."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Nontuberculous Mycobacterial Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • CD4 • CD8 • IFNG

Early life adversity promotes a milieu in favor of catabolic bone turnover in females: Mycobacterium vaccae NCTC 11659 proofs protective in preclinical studies. (PubMed, Brain Behav Immun) - "Finally, our clinical data indicate strong associations between ELA and development of an osteopenic/osteoporotic bone phenotype in postmenopausal women undergoing bone diagnostics. Together, our preclinical and clinical findings indicate that i) ELA negatively affects the bone, ii) these effects are specific for female sex, iii) the negative effects of ELA on female bone are associated with transient changes in the composition of the intestinal microbiome followed by long-lasting activation of the immune system and the HPA axis, together setting the stage for a facilitated catabolic bone turnover and development of an osteopenic/osteoporotic bone phenotype, iv) developing immunoregulatory approaches, such as repeated s.c. administrations with immunoregulatory microorganisms, have potential for prevention/treatment of ELA-related bone disorders."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Post-traumatic Stress Disorder • Psychiatry • Rheumatology • CTSK • IL6

Effects of repeated intragastric administrations with heat-inactivated Mycobacterium aurum DSM 33539 on the stress-induced aggravation of dextran sulfate sodium (DSS) colitis in C57BL/6N mice. (PubMed, Front Neurosci) - "In line with the latter, M. aurum DSM 33539 was further protective against the aggravating effects of stress on subsequent DSS colitis. Collectively, our findings confirm and extend previous findings from our group and suggest that the stress-protective effects reported for M. vaccae NCTC 11659 and M. vaccae ATCC 15483T are generalizable also to other NTM species."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Nontuberculous Mycobacterial Disease • Respiratory Diseases

The sex-specific effects of early life adversity and chronic psychosocial stress during adulthood on bone are mitigated by Mycobacterium vaccae NCTC 11659 in mice. (PubMed, Neuroimmunomodulation) - "Conclusion Our results support the hypotheses that the negative effects of ELA and CAS on bone are highly sex-dependent. Moreover, repeated s.c. administrations with immunoregulatory microorganisms might be a future therapeutic option for stress-related bone disorders."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Mental Retardation • Musculoskeletal Diseases • Orthopedics • Post-traumatic Stress Disorder • Psychiatry

Time course analysis of the effects of M. vaccae NCTC 11659 on gene expression in naïve or lipopolysaccharide-challenged BV2 microglial cells (Neuroscience 2024) - "Though previous work has made promising suggestions regarding the mechanism of action, the exact mechanism by which M. vaccae NCTC 11659 imparts its anti-inflammatory effects in BV2 cells remains unclear, and it remains possible that anti-inflammatory reprogramming takes more time than was allowed in previous studies. Thus, this experiment will analyze the effects of M. vaccae NCTC 11659 on BV2 murine microglial cells in a time-course manner, using intervals of 24 h, 72 h, and 168 h between M. vaccae NCTC 11659 and LPS exposures."

CNS Disorders

Therapeutic vaccines for advanced non-small cell lung cancer. (PubMed, Cochrane Database Syst Rev) - "Adding a vaccine resulted in no differences in overall survival, except for racotumomab, which showed some improvement compared to placebo, but the difference in median survival time was very small (1.4 months) and the study only included 176 participants. Regarding progression-free survival, we observed no differences between the compared treatments, except for TG4010, which may increase progression-free survival slightly. There were no differences between the compared treatments in serious treatment-related adverse events, except for SRL172 (killed Mycobacterium vaccae) added to chemotherapy, which was associated with an increase in the proportion of participants with at least one serious treatment-related adverse event, and OSE2101, which may decrease slightly the proportion of people having at least one serious treatment-related adverse event. These conclusions should be interpreted cautiously, as the very low- to moderate-certainty evidence prevents drawing solid ..."

Journal • Metastases • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Effects of Mycobacterium vaccae NCTC 11659 and Lipopolysaccharide Challenge on Polarization of Murine BV-2 Microglial Cells. (PubMed, Int J Mol Sci) - "In contrast, among LPS-challenged cells, although M. vaccae NCTC 11659 did not fully prevent the effects of LPS relative to vehicle-treated control conditions, it increased Arg1 mRNA expression, suggesting that M. vaccae NCTC 11659 induces an atypical microglial phenotype. Thus, M. vaccae NCTC 11659 acutely (within 48 h) induced immune-activating and microglial-priming effects when applied directly to murine BV-2 microglial cells, in contrast to its long-term anti-inflammatory and immunoregulatory effects observed on the CNS when whole-cell, heat-killed preparations of M. vaccae NCTC 11659 were given peripherally in vivo."

Journal • Preclinical • Inflammation • ARG1 • CCL2 • IL1B • IL6 • NLRP3

Effects of a soil Mycobacterium-derived lipid, 10(Z)-hexadecenoic acid, on murine dendritic cells: A mechanistic analysis (Neuroscience 2023) - "Mycobacterium vaccae NCTC 11659, a soil-derived mycobacterium with anti-inflammatory, immunoregulatory, and stress resilience effects is one such "Old Friend"...This suggests that Il6 expression in murine BMDCs is controlled in part by PPARα. These results further our understanding of the mechanism by which 10(Z)-HDA has its effects and of understanding host mycobacteria interactions."

Preclinical • CNS Disorders • Mood Disorders • Psychiatry • IL6 • PPARA

The effects of inescapable stress on leukocyte subpopulations in male rats previously treated with Mycobacterium vaccae NCTC 11659 (Neuroscience 2023) - "Prior administration of M. vaccae NCTC 11659 not only attenuated the increase of inflammatory monocytes, but caused an increase of NK cells. Our data suggest that M. vaccae NCTC 11659 may exert its immunomodulatory effects in part by reducing the number of inflammatory monocytes."

Preclinical • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • CD4 • CD8

Subcutaneous Mycobacterium vaccae ameliorates the effects of early life adversity alone or in combination with chronic stress during adulthood in male and female mice. (PubMed, Neurobiol Stress) - "Finally, our data support the hypothesis that female mice are more vulnerable to the additive effects of ELA and CAS than male mice and that s.c. M. vaccae administrations subsequent to ELA but prior to CAS are protective in both sexes. Taken together and considering the limitation that CAS in males and females was induced by different paradigms, our findings are consistent with the hypotheses that murine stress vulnerability during different phases of life is strongly sex dependent and that developing immunoregulatory approaches, such as repeated s.c. administrations with immunoregulatory microorganisms, have potential for prevention/treatment of stress-related disorders."

Combination therapy • Journal • Preclinical • Inflammation • Mood Disorders • Psychiatry

Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages. (PubMed, Int J Mol Sci) - "Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders."

Journal • Asthma • CNS Disorders • Immunology • Inflammation • Mental Retardation • Psychiatry • Pulmonary Disease • Respiratory Diseases • IL10 • IL12A • IL23A • TGFB1

Safety and efficacy of tuberculosis vaccine candidates in low- and middle-income countries: a systematic review of randomised controlled clinical trials. (PubMed, BMC Infect Dis) - "Further efficacy trials for M72/AS01 are warranted to include additional populations at risk where safety has been demonstrated. Further safety trials are needed for the remaining vaccine candidates to confirm safety in vulnerable populations."

Clinical • Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Mycobacterium vaccae protects against glucocorticoid resistance resulting from combined physical and psychosocial trauma in mice. (PubMed, Brain Behav Immun) - "In contrast, the protective effects of i.g. M. vaccae on the CSC-induced upregulation of TLR2 in neutrophils and the subsequent increase in basal and LPS-induced in vitro splenocyte viability seems to be indirectly mediated via the Treg compartment. These data highlight the potential for use of oral administration of M. vaccae NCTC 11659 to prevent stress-induced exaggeration of inflammation, a risk factor for development of stress-related psychiatric disorders."

IO biomarker • Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Mental Retardation • Psychiatry • TLR2 • TLR4

Effects of 10(Z)-hexadecenoic acid, a lipid isolated from Mycobacterium vaccae, a bacterium with anti-inflammatory, immunoregulatory, and stress resilience properties, on murine bone marrow-derived dendritic cells (BMDCs) following lipopolysaccharide (E. coli 0111: B4) challenge or control conditions (Neuroscience 2022) - "In this study we investigated the effects 10(Z)-hexadecenoic acid, a lipid isolated from a soil-derived “Old Friend”, Mycobacterium vaccae NCTC 11659, with anti-inflammatory, immunoregulatory, and stress resilience properties, on the lipopolysaccharide (LPS; E. coli 0111: B4)-induced inflammatory response and the LPS-induced intracellular signaling cascades associated with dendritic cell (DC) polarization in bone marrow-derived dendritic cells (BMDCs) using the murine NanoString Inflammation V2 platform, which allows quantification of expression of 254 inflammation-related genes...These data are consistent with the hypothesis that 10(Z)-hexadecenoic acid attenuates LPS induced inflammation in BMDCs. Together, these data are consistent with the hypothesis that 10(Z)-hexadecenoic acid is a potential intervention for prevention of anxiety disorders, mood disorders, and trauma and stressor-related disorders by reducing stress- or trauma-induced exaggeration of..."

Preclinical • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • CXCL10 • IL12A • IL1A • IL1B • IL6 • IRF7 • PACERR • PTGS2

Effects of Mycobacterium aurum DSM 33539 on biological signatures of stress-induced neuroinflammation and stress resilience in adult male rats (Neuroscience 2022) - "In contrast, immunization with whole cell, heat-killed preparations of Mycobacterium vaccae NCTC 11659 (recently reclassified as M. kyogaense sp...Here we show that immunization with M. aurum DSM 33539 prevented inescapable stress- (IS-) induced increases in hippocampal Il6 mRNA expression and prevented IS-induced exaggeration of anxiety-like defensive behavioral responses in the juvenile social exploration paradigm, assessed 24 h after exposure to IS in adult male rats. Future studies are required to fully characterize the mechanisms through which M. aurum DSM 33539 and closely related mycobacterial strains prevent stress-induced exaggeration of neuroinflammation and promote stress resilience."

Preclinical • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • IL6

Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner. (PubMed, Brain Behav Immun) - "Finally, in an auditory-cued fear conditioning paradigm exploring short-term memory and fear acquisition, immunization with M. vaccae did not prevent fear acquisition, either with or without exposure to inescapable stress, consistent with the hypothesis that M. vaccae NCTC 11659 has no effect on fear acquisition but enhances fear extinction. These data are consistent with the hypothesis that increased immunoregulation following immunization with M. vaccae NCTC 11659 promotes stress resilience, in particular by preventing stress-induced resistance to fear extinction, and may be a potential therapeutic target for trauma and stressor-related disorders such as PTSD."

Journal • CNS Disorders • Immunology • Inflammation • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

Evolutionary Aspects of Diverse Microbial Exposures and Mental Health: Focus on "Old Friends" and Stress Resilience. (PubMed, Curr Top Behav Neurosci) - "We highlight evidence that microbial signals that can drive immunoregulation arise from phylogenetically diverse taxa but are strain specific. Finally, we highlight Mycobacterium vaccae NCTC 11659, a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, as a case study of how single strains of bacteria might be used in a psychoneuroimmunologic approach for prevention and treatment of stress-related psychiatric disorders."

Journal • Allergy • Asthma • CNS Disorders • Depression • Immunology • Inflammation • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Pulmonary Disease • Respiratory Diseases

Effects of Mycobacterium vaccae NCTC11659 treatment on fear extinction in female rats in the fear-potentiated startle paradigm (Neuroscience 2021) - "Overall, the results of the current study suggest that M. vaccae has stress-resilient properties and may be useful as a treatment for PTSD. However, these results suggest that sex differences exist in emotional behavioral responses to Mycobacterium vaccae NCTC 11659 in the FPS paradigm.; Grant Support: CU Foundation"

Preclinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Rapidly Growing Mycobacterium Species: The Long and Winding Road from Tuberculosis Vaccines to Potent Stress-Resilience Agents. (PubMed, Int J Mol Sci) - "This historical narrative review is intended as a first step in exploring these mechanisms and provides an overview of preclinical and clinical studies on M. vaccae NCTC 11659 and related RGMs. The overall objective of this review article is to increase the comprehension of, and interest in, the mechanisms through which M. vaccae NCTC 11659 and related RGMs promote stress resilience, with the intention of fostering novel clinical strategies for the prevention and treatment of stressor-related disorders."

Journal • Review • CNS Disorders • Immunology • Infectious Disease • Inflammation • Mental Retardation • Psychiatry • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a "Two Hit" Stressor Model. (PubMed, Front Physiol) - "Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M...Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience."

Journal

Immunization with a heat-killed bacterium, Mycobacterium vaccae NCTC 11659, prevents the development of cortical hyperarousal and a PTSD-like sleep phenotype after sleep disruption and acute stress in mice. (PubMed, Sleep) - "Immunization with MV ameliorates a stress-induced sleep and behavioral phenotype that shares features with human posttraumatic stress disorder."

Journal • CNS Disorders • Immunology • Inflammation • Mood Disorders • Post-traumatic Stress Disorder • Sleep Disorder

Alzheimer's Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats. (PubMed, J Alzheimers Dis) - "M. vaccae alters host immune activity and lipid metabolism. These data are consistent with the hypothesis that microbe-host interactions may protect against possible infection-induced, inflammation-related cognitive impairments."

IO Biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Tuberculosis • IL4

Comparing the effects of two different strains of Mycobacterium vaccae, M. vaccae NCTC 11659 and M. vaccae ATCC 15483, on stress-resilient behaviors and lipid-immune signaling in rats. (PubMed, Brain Behav Immun) - "Analysis of mRNA expression, protein abundance, and flow cytometry data demonstrate overlapping but also unique effects of treatment with the two M. vaccae strains on immunological and metabolic signaling in the host. These data support the hypothesis that treatment with different M. vaccae strains may immunize the host against stress-induced dysregulation of physiology and behavior."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • IL6

DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial. (PubMed, Vaccine) - P2 | "A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted."

Clinical • Journal • P2b data • Infectious Disease • Tuberculosis

The potential of CBC-derived ratios (monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte) to predict or diagnose incident TB infection in Tanzanian adolescents. (PubMed, BMC Infect Dis) - P2 | "In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity."

Journal • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • Tuberculosis