Transmission of IgA and IgG Monoclonal Antibodies to Mucosal Fluids following Intranasal or Parenteral Delivery

Abstract

Background: The efficacy by which passive antibodies can reach the lungs could be important for the outcome of immunotherapy of respiratory pulmonary infections. We examined how transmission to a number of mucosal sites is affected by the route of inoculation. Methods: Transmission of newly raised IgA class Mabs against mycobacterial surface antigens to saliva, lung or vaginal lavage, bile and serum of BALB/c mice was compared with existing IgG Mabs. ELISA was used for testing body fluids obtained 1–24 h after intranasal or intravenous inoculation and 1–7 days following back-pack tumour growth of hybridomas. Results: Intranasal inoculation resulted in a rapid rise and high levels of both IgA and IgG class Mabs in lung lavage. In contrast, following intravenous Mab injection or back-pack tumour growth of hybridoma cells, effective lung transmission was observed for the IgG1 and IgG2b MAbs, but not for the IgA Mabs. The secretory component was acquired by the transmitted IgA MAbs in the mucosal fluids, but not in the serum. Nevertheless, the time course of mucosal IgA antibody levels was similar to that of the tested IgG Mabs. Furthermore, the relative proportion of transmission to saliva and bile varied between individual Mabs indicating a role of tissue-specific, immunoglobulin class-unrelated mechanisms. Conclusions: Intranasal, rather than parenteral inoculation of mice is required for the efficient delivery of IgA antibodies against respiratory pulmonary pathogens. Interestingly, IgA-secretory component complexing of intranasally applied Mabs did not significantly influence their persistence in the lungs.

Intranasal IFNγ extends passive IgA antibody protection of mice againstMycobacterium tuberculosislung infection

“…TBA61 IgA mAb against surface expressed α -crystallin homologue antigen (acr1, hsp16.3, hspX or 16 kD antigen) [11] was purified from hybridoma supernatants (CL-1000 cell culture device, Integra Biosciences, Letchworth, UK), using an acr1-Affigel 15 (Bio-Rad, Hemel Hempstead, UK) affinity column. Following affinity chromatography, the antibody preparation was passed through a Polymyxin B agarose column (Sigma, Poole, UK), in order to remove any contaminating LPS.…”

Immunotherapy of Tuberculosis with IgA and Cytokines

“…or parenteral administration [42] was more efficient for IgA, than for IgG mAbs. When comparing these mAbs for their protective c a p a c i t y i n B A L B / c m o u s e m o d e l o f M. tuberculosis infection, the IgA mAb TBA61, which is specific for the α-crystallin (Acr, 16 kDa) antigen, was superior to both an IgG1 of the same antigen and epitope specificity, and also to another IgA mAb, specific for the PstS1 (38 kDa) antigen [43].…”

“…TBA61 anti-Acr mAb generated and shown to be superior to IgG for transmission to lungs [42] 2004 TBA61 IgA induced a 10-fold inhibition of early M. tuberculosis infection in BALB/c mice; however, inhibition was transient [43] 2006 Co-administration of IgA and IFN- extended the duration of inhibition compared to IgA alone …”

Towards a New Challenge in TB Control: Development of Antibody-Based Protection

“…In tracheobronchial lavage, hsIgA was detected at 2 and 3 hours after inoculation in animals that received the hsIgA [51]. Similar studies were performed by Falero and colleagues with monoclonal antibodies of IgA and IgG class [52]. Following demostration that hsIgA could be detected in several biological secretions after intranasal administration, the protective effect of this formulation against M. tuberculosis challenge was evaluated.…”