Evidence that a primary anti-viral stimulation of the immune response by OM-85 reduces susceptibility to a secondary respiratory bacterial infection in mice

Abstract

BACKGROUND: Viral respiratory infections may promote bacterial super-infection decreasing the host immune response efficiency. However, using a mice model we recently demonstrated that preventive treatment with the bacterial extract OM-85 reduces the susceptibility to a secondary Streptococcus (S.) pneumoniae infection after influenza virus (I.V.) challenge. METHODS: To better characterize the efficacy of OM-85 against S. pneumoniae super-infection, a post-hoc analysis was conducted, comparing efficacy (survival) and morbidity signs (clinical score, body temperature and weight loss) in the OM-85 and the control (BLANC) groups of mice after: a) I.V. infection; b) primary S. pneumoniae infection and c) post-I.V. S. pneumoniae super-infection. RESULTS: After a sublethal I.V. dose, all mice stayed alive at day 5 and no differences in morbidity signs were detected between the OM-85 and the BLANC groups. However, OM-85 pretreatment led to a significantly reduction of the viral load in the lung on day 5 post viral infection and, on day 10, reduced neutrophilic inflammation while increasing influenza-specific CD8 + T-cell proportion in the airways. Conversely to viral infection, exposure to S. pneumoniae induced a dramatic reduction of survival, with no mice surviving on day 3 post infection in the BLANC group, whereas a partial protective effect was observed in OM-85 pre-treated mice (20% of mice surviving at day 3, and 10% at day 4 and 5). The morbidity data substantiated the survival results. Interestingly, in the "super-infection" study, when mice were exposed to a sublethal I.V. dose followed by a secondary S. pneumoniae infection, all mice died by day 4 in the BLANC group. In contrast, in the OM-85 treated group, the survival rate was 70% at day 4 and still 50% at day 5, with positive effects on the clinical scores and on the body temperature already detectable at days 1 and 2. CONCLUSIONS: The efficacy of OM-85 pre-treatment against S. pneumoniae super-infection reflects a strong and immediate immune reaction from the host, an event that can be explained in part by a "non-specific" activation of the immune system, a positive "immune effect" of the general OM-85- induced immune response against I.V.