Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies

Abstract

Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of childhood morbidity globally. Associated wheezing illness and asthma are still a clear unmet medical need. Despite the continuous progress in understanding the processes involved in their pathogenesis, preventive measures and treatments failed to demonstrate any significant disease-modifying effect. However, in the last decades it was understood that early-life exposure to microbes, may reduce the risk of infectious and allergic disorders, increasing the immune response efficacy. These results suggested that treatment with bacterial lysates (BLs) acting on gut microbiota, could promote a heterologous immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. This hypothesis has been supported by clinical and experimental studies showing the reduction of RTI frequency and severity in childhood after oral BL prophylaxis and elucidating the involved mechanisms. OM-85 is the product whose anti-viral effects have been most extensively studied in vitro, animal, and human cell studies and in translational animal infection/disease models. The results of the latter studies, describing the potential immune training-based activities of such BL, leading to the protection against respiratory viruses, will be reported. In response to human rhinovirus, influenza virus, respiratory syncytial virus and severe acute respiratory coronavirus-2, OM-85 was effective in modulating the structure and the functions of a large numbers of airways epithelial and immune cells, when administered both orally and intranasally.

Protection conferred by intraperitoneal Group AStreptococcusimmunization relies on macrophages and IFN-γ but not on concurrent adaptive immune responses

“…In contrast, in a study of trained immunity also employing intranasal immunizations, protection against subsequent infection was induced by several Gram-negative bacterial species, but not by S. aureus or S. pneumoniae [41]. Of note, the immunomodulant compound OM-85 is a bacterial lysate mix containing lyophilized fragments of 21 common bacterial pathogens, including GAS, S. aureus and S. pneumoniae , and is used clinically to treat children suffering from recurrent lower respiratory tract infections [42, 43]. The exact mechanism(s) of action of this treatment regimen has not yet been elucidated, but as protection is evident also for viral pathogens, the mechanism of protection is believed to at least partially be attributed to induced trained immunity.…”

Asthma in children—What's in the future

“…Immunomodulation offers the best chance of reducing the development of asthma and asthma exacerbations in the future. Many small trials have shown efficacy, and immunomodulation is known to enhance Th1 immunity and interferon production 15 . Although these studies have not been sufficient to persuade authorities to promote its widespread introduction, they have been impressive enough to generate support for several large, randomized, double‐blind, placebo‐controlled, immunomodulation clinical trials that are now nearing completion.…”

Diverging patterns in innate immunity against respiratory viruses during a lifetime: lessons from the young and the old

“…Orally administered bacterial lysates of mixed respiratory pathogenic bacteria have been used for decades to prevent RTIs [ 174 ] in children [ 175 , 176 ] and in vulnerable adults [ 177 – 179 ]. Infection incidence, duration and severity were studied in randomised clinical trials.…”