Recombinant secretory immunoglobulin A in passive immunotherapy: linking immunology and biotechnology.
The use of monoclonal antibodies has become routine in the research and diagnostic laboratories, but the potential of antibody molecules in public health and medical applications is still far from its maximum. Most infections begin at mucosal surfaces, and this is certainly not only a stroke of good fortune if mother's milk serves as a natural delivery vehicle for antibodies protecting the gastrointestinal tract of nursing infants. Mammary gland or other mucous secretions containing numerous antibody specificities provide an efficient mean to immediately protect a mucosal surface against pathogens, which have never been encountered by the host. From a public health perspective, topical passive immunization of mucosal surfaces with monoclonal antibodies can block entry and transmission of bacteria, viruses, fungi and parasites that infect humans, and thus defeat some key immune evasion strategies designed by many pathogens. The chief antibody on most mucosal surfaces is secretory immunoglobulin A (SIgA), a polypeptide complex comprising dimeric IgA, the connecting J chain, and the secretory component. The molecular stability, tetravalency, and strong anti-inflammatory properties make SIgA particularly well suited to fulfill the function of passive protective immunity when applied exogenously to mucosal surfaces. The review will give an overview of the basic concepts underlying mucosal immunity, present the molecular mechanisms whereby SIgA prevents mucosal infections, cover the last advances in the topic of recombinant SIgA production, and examine how structure-function relationship in SIgA will help designing molecules with novel properties for passive immunotherapy.
Corthésy
Blaise
B
Division d'Immunologie et d'allergie, R & D Laboratory, HO 05/1542, Avenue Pierre Decker 4, CH-1005 Lausanne. blaise.corthesy@chuv.hospvd.ch
D000818:Animals; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007071:Immunoglobulin A, Secretory / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*
D007071:Immunoglobulin A, Secretory; D011994:Recombinant Proteins