The Effect of Delipidated Deglycolipidated (DDMV) and Heat-killed Mycobacterium vaccae in Asthma

Abstract

Experimental and epidemiological evidence supports the hypothesis that exposure to mycobacteria has the potential to suppress the development of asthma and/or atopy and there are reports in the Chinese medical literature of repeated vaccination with inactivated BCG being effective in the management of asthma. Forty-three patients with stable moderately severe asthma who were skin prick test positive to house dust mite were randomized to receive two intradermal injections of either phosphate-buffered saline (placebo), heat-killed Mycobacterium vaccae (0.5 mg), or delipidated deglycolipidated Mycobacterium vaccae (DDMV) (0.05 mg). Markers of asthma severity were measured for 3 mo and blood eosinophil, IgE levels, and the T cell proliferative and cytokine responses were monitored. There were no significant differences between either treatment group and the placebo group for any of the outcome variables. There was also no difference between the treatment groups and placebo for eosinophil, IgE levels, or the T cell proliferative and cytokine response. The results indicate no effect of low dose intradermal DDMV or M. vaccae on asthma severity in patients with established asthma.

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

“…The most plausible explanation for the relatively small effects in the current study may be that higher and/or more frequent doses have to be given for greater efficacy. A study by SHIRTCLIFFE et al [21], using half the dose applied in the current study and a different strain of M. vaccae (ATCC 15483), failed to reach statistical significance with regard to the number of clinical asthma outcomes.…”

“…The timing of the challenge in relation to the injection of SRL172 was based on the attenuating effect of SRL172 in the murine ovalbumin-sensitised mouse seen 3 weeks after administration of M. vaccae [17]. However, recent evidence suggests that 3 weeks was too soon to seek maximal effect [21]. It is also possible that the immunomodulatory capacity of SRL172 varies considerably from mildly to highly allergic individuals.…”

Streptococcus pneumoniaeinfection suppresses allergic airways disease by inducing regulatory T-cells

“…This work has drawn on widespread acceptance of the hygiene hypothesis, which is a well recognised, if oversimplified, link between infection and allergy. Administration of mycobacteria and other Th1-inducing infectious agents for the treatment of asthma in humans has given disappointing results, and successful results were dependent on the age of study subjects [4,12,14]. The therapeutic use of S. pneumoniae antigens that may prevent Th2 and eosinophil development and mobilisation by a different mechanism, i.e.…”

“…Administration of mycobacterial components inhibits allergic airway disease (AAD); however, the efficacy of mycobacterial treatment in preventing allergic diseases in human trials has been varied, with decreases in the severity of atopic dermatitis but no affect on allergic asthma [11][12][13].…”

Mycobacteria, genes and the ‘hygiene hypothesis’

“…]). Studies using BCG [51] or heat-killed M. vaccae [52] therapeutically in established asthma or atopic dermatitis [53], however, showed beneficial effects of mycobacterial treatment, although the effect of M. vaccae in asthma patients was not confirmed [54]. These contrasting results might be explained by the fact that a lot of variables were different in these studies, such as the age at and the frequency of vaccination with mycobacteria, the BCG strain used and the varying natural exposure to mycobacteria (including M. tuberculosis) or allergens [55].…”