Ismigen can Provide Protection Against Viral Antigens

Potential role of Ismigen® as adjuvant in the prevention of influenza episodes

Mario Cazzola Unit of Respiratory Clinical Pharmacology Department of Internal Medicine University of Rome “Tor Vergata” Rome, Italy

Bacterial immunostimulation has been advocated as a management strategy in COPD for the purposes of preventing acute exacerbations. The recent scientific opinion supports the possibility that bacterial immunostimulants might be considered as possible adjuvants in the prevention of influenza episodes, and prolong antibody response to influenza vaccine strains. In fact, some data indicate interesting synergic effects of bacterial extracts in extending the immunological response to influenza vaccine in COPD patients [1].

This is intriguing information considering that influenza A virus (IAV) infections represent a significant public health threat, particularly in the case of children, the elderly, and those with underlying diseases, all of whom are at a significantly increased risk for disease complications and death following IAV infection [2]. This is now even more important because the recent appearance of IAV strains with pandemic potential, such as H1N1 “swine flu” and H5N1 avian influenza, have highlighted the importance of research into IAV infections and the innate and adaptive immune responses that control and eliminate infection [2].

Although adaptive immunity is essential for the clearance of IAV infection, innate immune cells also play essential roles in the control of IAV. In recent years, it has become increasingly apparent that innate immune cells, including natural killer cells, alveolar macrophages, and dendritic cells are essential following IAV in the direct control of viral replication or in the induction and regulation of virus-specific adaptive immune responses [2]. By assessing the different intervention mechanisms of the different cells committed with the immune response after the aggression by a virus, we can infer that the main objective of an effective prophylactic vaccination strategy aims to potentiate the function of dendritic cells, an important link between phagocyte cells and the activation of lymphocyte and therefore an interface between innate immunity and specific one.

There is solid evidence that stimulation with a complex mixture of bacterial products induces a high level of resistance against a virulent pathogen [3]. It is likely that this acquired protection is due to innate immune mechanisms because it occurs too rapidly for an adaptive immune response, and the challenge is not cognate to the stimulus. The lysate has the potential to stimulate lung defenses through multiple innate immune mechanisms simultaneously, such as formyl peptide receptors, complement receptors, lectin pathways, and Toll-like receptors (TLRs) [3]. The interaction between bacterial structures and TLRs results in the activation of monocytes, their differentiation to immature dendritic cells and the following maturation to mature dendritic cells, able to be considered a suitable professional antigen presenting cell [4]. On the contrary, stimulation of individual pathways may not induce a comparable level or spectrum of protection because individual pathways may either differentially activate pathogen-specific effector mechanisms or synergistically activate a single mechanism [3].

A body of evidence supports the concept that Ismigen® is effective in the prophylaxis of lower respiratory tract infections [5]. Data obtained in vitro, by using the cytofluorimetry technique, have proven that Ismigen® is a polyvalent mechanical bacterial lysate (PMBL) prepared by bacteria (S. aureus, S. pyogenes, S. viridans, K. ozaenae, H. influenzae serotype B, M. catarrhalis, and S. pneumoniae) obtained by mechanical lysis, can induce the activation of dendritic cells [6] and, in general, it can promote the activation of innate immune response and specific ones both in vitro and in vivo [7]. This is a really intriguing finding. It indicates that the use of Ismigen® might be advocated for also preventing influenza episodes. Obviously, a dedicated large study is mandatory for confirming this hypothesis, but the real life and clinical trials [8] clearly demonstrate that this use abates the number of respiratory infections, which means also a reduction in influenza episodes with respiratory involvement.

In any case, I believe that the documentation that stimulation of lung innate immunity can be therapeutically combined with an antiviral medication after influenza infection to improve survival more than either treatment alone [9] is important and opens a new door for the use of Ismigen®.

References

1. Centanni S, Pregliasco F, Bonfatti C, Mensi C, Tarsia P, Guarnirei R, et al. Clinical efficacy of a vaccine-immunostimulant combination in the prevention of influenza in patients with chronic obstructive pulmonary disease and chronic asthma. J Chemother 1997;9:273–8
2. McGill J, Heusel JW, Legge KL. Innate immune control and regulation of influenza virus infections. J Leuk Biol 2009;86:DOI:10.1189/jlb.050936
3. Clement CG, Evans SE, Evans CM, Hawke D, Kobayashi R, Reynolds PR, Moghaddam SJ, Scott BL, Melicoff E, Adachi R, Dickey BF, Tuvim MJ. Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice. Am J Respir Crit Care Med. 2008;177:1322-30
4. Braido F, Tarantini F, Ghiglione, V, Melioli G, Canonica GW. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections. Int J Chron Obstruct Pulmon Dis. 2007; 2: 335–345
5. Cazzola M, Rogliani P, Curradi G. Bacterial extracts for the prevention of acute exacerbations in chronic obstructive pulmonary disease: a point of view. Respir Med 2008;102:321-7
6. Cangemi G, Morandi B, Ferlazzo G, Melioli G. The maturation of dendritic cells mediated by a polivalent mechanical bacterial lysate (PBML) results in the secretion of cytokines inducing an anti-bacterial polarization of the locoregional immune-response. Eur Respir J 2004;24, Sup 48.
7. Fuggetta MP, Lanzilli G. Attivazione delle risposte immunitarie mediante vaccini batterici Europ Respir News 2007;15:69-77
8. Rossi S, Tazza R. Efficacy and safety of a new immunostimulating bacterial lysate in the prophylaxis of acute lower respiratory tract infections. A randomised, open, controlled clinical trial. Arzneimittelforschung 2004;5450-6
9. Tuvim MJ, Evans SE, Clement CG, Dickey BF, Gilbert BE (2009) Augmented Lung Inflammation Protects against Influenza A Pneumonia. PLoS ONE 4(1):e4176. doi:10.1371/journal.pone.0004176

• Polyvalent Bacterial Mechanical Lysates (PBML) had the capacity of inducing the maturation of monocyte-derived dendritic cells in a dose-dependent manner with highly specific IgG and IgA especially IgG1 response was evidenced suggesting a Th2 polarization. This regulation could decrease the likelihood of chronic inflammatory pathology in treated patients. (Cangemi et al)
  Source -
  1. The maturation of dendritic cells
     

• Oral Ismigen was found to induce non specific immuno stimulating activity against viral antigens in Swiss CD1 mice which resulted in reduction in the mortality compared to control groups.
  (Chiara et al 1983)
  Source -
  1. ISMIGEN_Effective against influenza virus

• It increases the number of immune cells ready to fight infections.
• Stimulates innate immunity by activating macrophages able to recognize and kill each non-self cell that help to phagocytose pathogens stimulates the secretion of TNFα by macrophages.
• Stimulates acquired immunity through the activation of B lymphocytes and the release of antibodies.
• ProbioKid® is an optimal combination of 3 strains (Lactobacillus Rosell-52, Bifi dobacterium Rosell-71, Bifi dobacterium Rosell-33) and a prebiotic (Fructooligosaccharrides).
• This allows for a synergistic effect between the bacteria and a synbiotic effect with the prebiotic.
• ProbioKid® supplementation showed a 25% decrease in the risk of common infectious disease incidences and a 40% reduction in the number of children who lost at least one day of school because of an adverse health event.

Source -
1. Sales Aid PROBIOKID
2. PRO118 Probiokid mother leaflet
3. Probiokid Comic

• Vitamin D appears to be involved in a rapidly increasing number of infections, tuberculosis, bacterial vaginitis, sepsis, HIV, and now the common cold and influenza have become a major concern.
• Swine flu, H1N1, has killed thirty-six children in U.S. and analysis of CDC data indicates Vitamin D deficient children at higher risk of death.
• This is evident from the fact that two-thirds of the children who died were having epilepsy, cerebral palsy, and mental retardation which are associated with childhood Vitamin D deficiency.
Read More