UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain.

Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials.

Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation.

Polyvalent bacterial lysates have been in use for decades for prevention and treatment of respiratory infections with reported clinical benefits. However, besides claims of broad immune activation, the mode of action is still a matter of debate. The lysates, formulated with the main bacterial species involved in respiratory infections, are commonly prepared by chemical or mechanical disruption of bacterial cells, what is believed influences the biological activity of the product. Here, we prepared two polyvalent lysates with the same composition but different method of bacterial cell disruption and evaluated their biological activity in a comparative fashion. We found that both bacterial lysates induce NF-kB activation in a MyD88 dependent manner, suggesting they work as TLR agonists. Further, we found that a single intranasal dose of any of the two lysates, is sufficient to protect against pneumococcal pneumonia, suggesting that they exert similar biological activity. We have previously shown that protection against pneumococcal pneumonia can also be induced by prior S. pneumoniae sub lethal infection or therapeutic treatment with a TLR5 agonist. Protection in those cases depends on neutrophil recruitment to the lungs, and can be associated with increased local expression of IL-17A. Here, we show that bacterial lysates exert protection against pneumococcal pneumonia independently of neutrophils, IL-17A or Caspase-1/11 activation, suggesting the existence of redundant mechanisms of protection. Trypsin-treated lysates afford protection to the same extent, suggesting that just small peptides suffice to exert the protective effect or that the molecules responsible for the protective effect are not proteins. Understanding the mechanism of action of bacterial lysates and deciphering the active components shall allow redesigning them with more precisely defined formulations and expanding their range of action.

Rol de los lisados bacterianos en asma, evidencia y proyección con especial referencia a OM-85 / Role of bacterial lysates in asthma, evidence and projection with special reference to OM-85

Existen diversos lisados bacterianos, siendo OM-85 (Broncho-Vaxom®) el que posee mayor evidencia en cuanto a su rol inmunoprotector sobre infecciones respiratorias en población pediátrica. Sus mecanismos de acción producen efectos inmunomoduladores que potencialmente podrían prevenir el asma en etapas precoces de la vida, actuar sobre la disminución de crisis y ser un aporte a la terapia convencional del asma. Este artículo expone las principales evidencias en relación con estos compuestos, con enfoque en la actualidad y el desarrollo futuro, en especial sobre OM-85.

There are several bacterial lysates, being OM-85 (Broncho-Vaxom®) the one with the greatest evidence regarding its immunoprotective role on respiratory infections in the pediatric population. Its mechanisms of action produce immunomodulatory effects that could potentially prevent asthma in early stages of life, act on the reduction of crisis and be a contribution to conventional asthma therapy. This article shows the main evidences in relation to these compounds, the current focus and future development, especially on OM-85.

Clinical and Immunological Benefits of OM-85 Bacterial Lysate in Patients with Allergic Rhinitis, Asthma, and COPD and Recurrent Respiratory Infections.

PURPOSE: The aim of this study was to evaluate the efficacy of OM-85 in reducing the incidence of respiratory tract infections (RTIs) in patients with allergic rhinitis, asthma, or chronic obstructive pulmonary disease (COPD), and its effect on immunological parameters, namely serum and secretory IgA levels. METHODS: This was an open-label, prospective, sequential study which included 84 consecutive patients aged 16-65 years, who presented with recurrent (three or more) respiratory infections during the year prior to study entry. In the first year of the study, patients received standard optimized care (SOC), according to their underlying disease condition (asthma, allergic rhinitis, or COPD). In the following year, patients received treatment with OM-85 oral bacterial lysate (one 7 mg capsule daily for ten consecutive days per month, for 3 months), with a 6-month follow-up. Medical history, clinical symptoms, serum, and secretory IgA levels, and the number of infections and exacerbations were evaluated before and after treatment. RESULTS: There was a decrease in the total number of RTIs before the OM-85 treatment period (SOC only) compared to the year before the study start [69/266 (corresponding to a 74 % reduction)] and an additional decrease [38/69 (corresponding to a 45 % reduction)] after OM-85 treatment; p < 0.05. There was also a significant reduction in the total number of exacerbations related to the patients' underlying medical conditions, which decreased from 55 to 35 during OM-85 (+SOC) treatment, corresponding to a reduction of 36 %. In addition, an increase in serum and secretory IgA levels which coincided with the administration of OM-85 was observed. CONCLUSIONS: Our results showed the clinical benefits of OM-85 in reducing RTIs and exacerbations of the underlying medical condition, in patients with allergic rhinitis, asthma, or COPD.