Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial Extract.
Bottom Line: We show that oral administration with the bacterial extract, OM-85, leads to a maturation of dendritic cells and B-cells characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL.The protection was associated with enhanced polyclonal B-cell activation and release of antibodies that were effective at neutralizing the virus.Taken together, these data show that oral administration of bacterial extracts provides sufficient mucosal immune stimulation to protect mice against a respiratory tract viral infection and associated sequelae.
Affiliation: OM Pharma SA Geneva , Geneva , Switzerland.
Secondary bacterial infections following influenza infection are a pressing problem facing respiratory medicine. Although antibiotic treatment has been highly successful over recent decades, fatalities due to secondary bacterial infections remain one of the leading causes of death associated with influenza. We have assessed whether administration of a bacterial extract alone is sufficient to potentiate immune responses and protect against primary infection with influenza, and secondary infections with either Streptococcus pneumoniae or Klebsiella pneumoniae in mice. We show that oral administration with the bacterial extract, OM-85, leads to a maturation of dendritic cells and B-cells characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL. Improved immune responsiveness against influenza virus reduced the threshold of susceptibility to secondary bacterial infections, and thus protected the mice. The protection was associated with enhanced polyclonal B-cell activation and release of antibodies that were effective at neutralizing the virus. Taken together, these data show that oral administration of bacterial extracts provides sufficient mucosal immune stimulation to protect mice against a respiratory tract viral infection and associated sequelae.
No MeSH data available.
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Mentions: To further dissect the possible mechanism through which OM-85 protects mice against influenza infection and subsequent secondary bacterial infection, we next characterized its effect upon B-cells. In an approach similar to the DC analysis, we stimulated splenocytes with different concentrations of OM-85 and assessed their activation state. Similar to the DC response, CD40 (Figure 4A) and CD86 (Figure 4B) were upregulated in a dose-dependent manner on B1 B-cells, Follicular B (FB) cells and marginal zone (MZ) B-cells. However, contrary to the DCs, these B-cell populations exhibited no significant changes in their expression of ICOSL except, to a minor extent, in MZ B-cells (Figure 4C). In order to determine whether these OM-85 driven changes in B-cell maturation had consequences in vivo, we administered OM-85 for 10 days by gavage as performed previously (Figure 1A), and then assessed IgG and IgA in the serum and airways of mice. OM-85 treatment alone led to a statistically significant increase in the levels of IgG detected in the serum of mice and trends toward increased IgA and IgG in the airways (Figure 5A). Of note, however, there was a statistically significant increase in IgA isolated from the serum or airways that bound to influenza antigens (Figure 5B). This was particularly intriguing because the OM-85 treated mice had not been infected with the virus in this setting. Moreover, antibodies that bound respiratory syncytial virus (RSV) were also detectible in the OM-85 treated groups (Figure 5C). These data indicate that OM-85 treatment had led to a polyclonal B-cell activation that resulted in release of antibodies against multiple antigens. Although we could detect comparably higher levels of these antibodies in OM-85 as compared to control treated mice, their relevance was unclear. Thus, to assess whether these polyclonal antibodies had functional implications, we tested their ability to limit influenza virus infection. Indeed, in an in vitro virus neutralization assay, heat-inactivated serum or BAL fluid from OM-85 treated mice was effective at limiting influenza infection (Figure 5D). Taken together, these data indicate that OM-85 can act to protect mice against influenza infection by enhancing B-cell activation and release of broadly protective antibodies that help to protect the host against infection.
No MeSH data available.