Passive protection with immunoglobulin A antibodies against tuberculous early infection of the lungs.
We report on a new approach toward protection against tuberculosis, based on passive inoculation with immunoglobulin A (IgA) antibodies. In a mouse model of tuberculous lung infection, intranasal inoculations of mice with an IgA monoclonal antibody (mAb) against the alpha-crystallin antigen of Mycobacterium tuberculosis reduced up to 10-fold the lung bacterial counts at nine days after either aerosol- or intranasal challenge. This effect involved synergism between mAb inoculations shortly before and 3 days after infection. Monomeric IgA reduced the colony-forming unit counts to the same extent as the polymeric IgA, suggesting antibody targeting to Fcalpha, rather than poly-immunoglobulin receptors on infected lung macrophages. The protective effect was of short duration, presumably due to the rapid degradation of the intranasally applied IgA. Our results provide evidence of an alternative approach which could be further developed toward immunoprophylaxis against tuberculosis in immunocompromised subjects.
Health Protection Agency, Porton Down, Centre for Applied Microbiology and Research (CAMR), Salisbury, UK.
Ann
A
Williams
Rajko
R
Reljic
Irene
I
Naylor
Simon O
SO
Clark
Gustavo
G
Falero-Diaz
Mahavir
M
Singh
Stephen
S
Challacombe
Philip D
PD
Marsh
Juraj
J
Ivanyi
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015169:Colony Count, Microbial / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D007116:Immunization, Passive / Q000379:methods*; D007070:Immunoglobulin A / Q000008:administration & dosage / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D000336:Aerosols; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; C034639:polymeric IgA