Mucosal immunotherapy of tuberculosis: is there a value in passive IgA?
Immunotherapeutic approaches, which have been considered for tuberculosis (TB), include immuno-potentiating or suppressing agents, cytokines, antibodies, DNA vaccines, non-pathogenic mycobacteria and mycobacterial extracts. While most or all of these potential agents showed at least some degree of promise in various experimental models, few progressed to clinical trials, yielding only moderately encouraging, though controversial results. Consequently, further research is required, as the need for an immunological agent, adjunct to chemotherapy, remains strongly justified. Its purpose is to shorten the currently protracted (6-9 months) drug treatment and thus increase compliance rates, which are most disappointing in areas with the highest disease prevalence. Using a mouse model of Mycobacterium tuberculosis (Mtb) infection, we recently reported, that an intranasally given monoclonal IgA antibody significantly reduced the bacterial load in the infected lungs, and that this protective effect of IgA could be further extended by co-inoculation with interferon gamma (IFNgamma). In this review, we describe the main features of IgA and its cellular receptors, the extent and possible mechanisms of passive vaccination with an IgA monoclonal antibody against the alpha-crystallin antigen of Mtb and discuss the potentials of this approach in the wider context of immunotherapy of TB.
Reljic
Rajko
R
Mucosal Biology Research Group, Guy's Hospital Campus of King's College London, UK.
Williams
Ann
A
Ivanyi
Juraj
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D018928:Immunity, Mucosal; D007116:Immunization, Passive / Q000379:methods*; D007070:Immunoglobulin A / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use; D051379:Mice; D011961:Receptors, Fc / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D007371:Interferon-gamma