Bacterial cell wall components as immunomodulators—II. the bacterial cell wall extract OM-85 BV as unspecific activator, immunogen and adjuvant in mice

doi:10.1016/S0192-0561(97)00055-6

International Journal of Immunopharmacology

Volume 19, Issues 9–10, September–October 1997, Pages 551-558

International Journa...

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Abstract

The bacterial extract Broncho-Vaxom used for the prevention and treatment of recurrent respiratory tract infections is an immunomodulator in vitro and in vivo, as determined in a murine model. The extract acts, on the one hand, as macrophage activator and polyclonal B-lymphocyte stimulant. On the other hand, after repeated intraperitoneal or oral immunizations, the extract is immunogenic, inducing serum IgG binding to the bacterial strains used for the preparation of the extract. On bacteria, the sera recognize the cell wall components porin, lipoprotein/lipopeptide and murein. The bacterial extract also exhibits adjuvant properties when applied in mixture with antigens, such as TNP-BSA or an influenza vaccine preparation. The unspecific and the immunospecific stimulatory effect of the extract as well as its adjuvant properties could be of importance for understanding its therapeutic effect.

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Cited by (15)

Enhanced antimicrobial activity of novel synthetic peptides derived from vejovine and hadrurin
2013, Biochimica et Biophysica Acta - General Subjects
Citation Excerpt :
The variability obtained in the MIC assays (Tables 3 and 4) could be explained by taking into consideration the differences in the composition of the outer membrane of the bacterial strains, conferring a barrier against different antibacterial agents. Additional literature discussing this point can be found in [45–48]. The properties of the peptides such as amphipathicity, hydrophobicity and charge enable them to act selectively toward prokaryotic membranes.
Microbial antibiotic resistance is a challenging medical problem nowadays. Two scorpion peptides displaying antibiotic activity: hadrurin and vejovine were taken as models for the design of novel shorter peptides with similar activity.
Using the standard Fmoc-based solid phase synthesis technique of Merrifield twelve peptides (18 to 29 amino acids long) were synthesized, purified and assayed against a variety of multi-drug resistant Gram-negative bacteria from clinical isolates. Hemolytic and antiparasitic activities of the peptides and their possible interactions with eukaryotic cells were verified. Release of the fluorophore calcein from liposomes treated with these peptides was measured.
A peptide with sequence GILKTIKSIASKVANTVQKLKRKAKNAVA), and three analogs: Δ(Α29), Δ(K12-Q18; Ν26−Α29), and K4N Δ(K12-Q18; Ν26−Α29) were shown to inhibit the growth of Gram-negative (E. coli ATCC25922) and Gram-positive bacteria (S. aureus), as well as multi-drug resistant (MDR) clinical isolated. The antibacterial and antiparasitic activities were found with peptides at 0.78 to 25 μM and 5 to 25 μM concentration, respectively. These peptides have low cytotoxic and hemolytic activities at concentrations significantly exceeding their minimum inhibitory concentrations (MICs), showing values between 40 and 900 μM for their EC₅₀, compared to the parent peptides vejovine and hadrurin that at the same concentration of their MICs lysed more than 50% of human erythrocytes cells.
These peptides promise to be good candidates to combat infections caused by Gram-negative bacteria from nosocomial infections.
Our results confirm that well designed synthetic peptides can be an alternative for solving the lack of effective antibiotics to control bacterial infections.
The bacterial extract OM-85 BV protects mice against Influenza and Salmonella infection
2010, International Immunopharmacology
The bacterial extract OM-85 BV has been shown to provide protection against recurrent respiratory infections. We here investigated its efficacy against viral and bacterial infections in murine models. We first evaluated the role of OM-85 BV protecting from an A/PR/8/34 (H1N1) influenza virus infection. In a group treated with 1.75 mg/mouse OM-85 BV all animals survived, compared to 70% in the untreated control group and a group treated with a lower dosage. In addition, the appearance of clinical signs was delayed, their intensity was decreased, and they disappeared faster; also a marked increase in the influenza hemagglutination inhibition antibody level was observed. Since bacterial infections often superimpose viral lung infections, we also investigated on the protection of mice from a Salmonella typhimurium infection after the oral administration of OM-85 BV. Here, 100% of the OM-85 BV treated animals survived compared to 58% of the untreated control group. The mechanism of protection was further investigated: OM-85 BV acts, on the one hand, as an immunogen: the repeated administration of OM-85 BV induced a marked increase in serum antibody levels recognizing pathogenic bacterial strains. On the other hand, the extract acts as a stimulator of the nonspecific macrophage, monocyte, dendritic cell, and granulocyte response. Our findings demonstrate the antimicrobial activity of OM-85 BV against infections, as also has been shown in clinical studies.
Prospective, Randomized Comparison of OM-85 BV and a Prophylactic Antibiotic in Children with Recurrent Infections and Immunoglobulin A and/or G Subclass Deficiency
2003, Current Therapeutic Research - Clinical and Experimental
Patients with immunoglobulin (Ig)A and/or IgG subclass deficiency may be asymptomatic or may have recurrent, mainly respiratory infections.
This study compared the clinical efficacy and tolerability of prophylactic therapy with either the oral immunomodulator bacterial extract OM-85 BV or benzathine penicillin G (BPG) in the prevention of recurrent infections in symptomatic patients.
In this 26-month, prospective, randomized study conducted at the Department of Pediatric Immunology, Ege University (Izmir, Turkey), children aged 1 to 12 years with recurrent infections and IgA and/or IgG subclass deficiency were enrolled. After an initial 12-month control period, patients were randomized to receive OM-85 BV or BPG. OM-85 BV (3.5-mg capsule) was given once daily for the first 10 days of each month for the first 3 months of the study. IM injections of BPG were given at a dose of 1.2 million units (for patients with body weight > 27 kg) or at a half-dose (for patients with body weight ≤27 kg) every 3 weeks for 12 months. In nonresponders (ie, those who continued to have recurrent infections at 12-month follow-up), IV immunoglobulin (IVIG) replacement therapy at 400 mg/kg body weight was given every 4 weeks for an additional 12 months. The results of IVIG therapy were assessed by the authors using clinical observation. Adverse effects and adverse drug reactions were documented by the authors for each vaccine, prophylactic therapy, and IVIG.
A total of 91 children (56 boys, 35 girls; mean [SD] age at the start of the control period, 46.4 [31.0] months) were enrolled. Of these, 44 were randomized to the OM-85 BV group and 47 to the BPG group. The year before prophylactic therapy, the mean (SD) number of reported infections was 10.7 (3.6) and the mean (SD) number of antibiotic courses was 9.7 (3.6) (OM-85 BV group: mean [SD] number of reported infections, 10.5 [3.3]; mean (SD) number of antibiotic courses, 9.3 [3.3]; BPG group: mean [SD] number of reported infections, 10.8 [3.9], mean (SD) number of antibiotic courses, 10.1 [3.9]). At 12 months, the number of infections and antibiotic courses decreased significantly in the entire study population, but the between-group difference was not significant. Five patients in each group (OM-85 BV group, 11.4%; BPG group, 10.6%) were considered nonresponders and received IVIG treatment. Compared with responders, nonresponders were significantly younger (mean [SD] age, 34.40 [21.70] months vs 52.65 [30.52] months; P = 0.036) and had lower serum IgG (P<0.001), IgG1 (P = 0.006), IgG2 (P = 0.003), IgG3 (P = 0.035), and IgM (P = 0.008) levels and antibody responses to tetanus toxoid and Haemophilus influenzae type b (Hib) vaccines (P = 0.036 and 0.013, respectively). At 12-month follow-up, a protective effect of the prophylactic IVIG therapy was seen, with a statistically significant reduction in the number of infections to 3.3 (2.4) and in the number of antibiotic courses to 2.7 (2.5) (both P = 0.005).
In this study population of children with recurrent infections and IgA and/or IgG subclass deficiency, prophylactic therapy with either OM-85 BV or an antibiotic significantly decreased the number of infections per year. In addition, nonresponders benefited from IVIG replacement therapy.
Mycobacterium tuberculosis: Drug resistance, virulence and possible solutions
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The immunomodulatory activity of secondary metabolites isolated from Streptomyces calvus on human peripheral blood mononuclear cells
2016, British Journal of Biomedical Science
OM85-BV induced the productions of IL-1β, IL-6, and TNF-α via TLR4- and TLR2-Mediated ERK1/2/NF-κB Pathway in RAW264.7 Cells
2014, Journal of Interferon and Cytokine Research

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International Journal of Immunopharmacology

Abstract

References (16)

Upregulation of adhesion molecules induced by Broncho-Vaxom on phagocytic cells

Int. J. Immunopharmac.

Stimulation by a bacterial extract (Broncho-Vaxom) of the metabolic and functional activities of murine macrophages

Int. J. Immunopharmacol.

Enhancement of protection against Salmonella infection in mice mediated by a synthetic lipopeptide analogue of bacterial lipoprotein in Salmonella typhimurium vaccines

Zbl. Bakt.

Biological activity of bacterial surface components: bacterial extracts and defined bacterial cell wall components as immunomodulators

Lung

Biological activity of bacterial surface components

Biological activity of bacterial cell wall components

Mucosal Immunity—A Major Adaptive Defence Mechanism

Behring Inst. Mitt.

L-arginine-dependent nitric oxide formation and nitrite release in bone marrow-derived macrophages stimulated with bacterial lipopeptide and lipopolysaccharide

Immunol.

Cited by (15)

Enhanced antimicrobial activity of novel synthetic peptides derived from vejovine and hadrurin

The bacterial extract OM-85 BV protects mice against Influenza and Salmonella infection

Prospective, Randomized Comparison of OM-85 BV and a Prophylactic Antibiotic in Children with Recurrent Infections and Immunoglobulin A and/or G Subclass Deficiency

Mycobacterium tuberculosis: Drug resistance, virulence and possible solutions

The immunomodulatory activity of secondary metabolites isolated from Streptomyces calvus on human peripheral blood mononuclear cells

OM85-BV induced the productions of IL-1β, IL-6, and TNF-α via TLR4- and TLR2-Mediated ERK1/2/NF-κB Pathway in RAW264.7 Cells