title: 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.
authors.affiliation: Department of Oral Medicine and Pathology, GKT School of Medicine and Dentistry Guy's Hospital, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Falero-Diaz
authors.forename: S
authors.initials: S
authors.lastname: Challacombe
authors.forename: D
authors.initials: D
authors.lastname: Rahman
authors.forename: M
authors.initials: M
authors.lastname: Mistry
authors.forename: G
authors.initials: G
authors.lastname: Douce
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: A
authors.initials: A
authors.lastname: Acosta
authors.forename: J
authors.initials: J
authors.lastname: Ivanyi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology / Q000493:pharmacokinetics*; D000942:Antigens, Bacterial / Q000276:immunology; D001646:Bile / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D018928:Immunity, Mucosal; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism*; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012463:Saliva / Q000276:immunology / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C072681:Mycobacterium tuberculosis antigens