||Polyvalent Bacterial Mechanical Lysate
Ismigen®, Respibron®, Vaxtab®, Pulmigen®, Immubron®
Ismigen can Provide Protection Against Viral Antigens
Potential role of Ismigen® as adjuvant in the prevention of
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 .
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 . 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
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 . 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 . 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) . 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 .
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 .
A body of evidence supports the concept that Ismigen® is effective in the
prophylaxis of lower respiratory tract infections . 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  and, in general, it can promote the activation of innate
immune response and specific ones both in vitro and in vivo . 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  clearly demonstrate that this use abates the number of respiratory
infections, which means also a reduction in influenza episodes with respiratory
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  is
important and opens a new door for the use of Ismigen®.
- 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
- 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
- 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
- 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
- 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
- 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.
- Fuggetta MP, Lanzilli G. Attivazione delle risposte immunitarie mediante
vaccini batterici Europ Respir News 2007;15:69-77
- 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.
- 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)
- 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)
- ISMIGEN_Effective against influenza virus
ProbioKid® Boosts the Body’s Natural Defenses
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Vitamin D is a Big Factor in H1N1 :
- 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.