Human polymeric IgA is superior to IgG and single-chain Fv of the same monoclonal specificity to inhibit urease activity associated with Helicobacter pylori.
Helicobacter-induced gastritis is considered nowadays an epidemic, the prevalence of which is one of the highest world-wide (70%), with as much as 40% of the population in industrialized countries. Helicobacter pylori (H. pylori) antigens (Ag) capable to elicit a protective immune response in animal models have been identified, but these antigens have not been shown to be strongly immunogenic when administered to humans. Due to their stability in the gastric environment and avidity, passive administration of secretory immunoglobulin A (SIgA) antibodies (Ab) targeting protective Ag might be particularly relevant as a substitute or complement to current therapies. To this aim, we have designed expression vectors to convert a scFv polypeptide specific for H. pylori urease subunit A into human IgG, polymeric IgA (IgAp/d) and SIgA. Purified proteins show proper binding characteristics toward both the native and denatured forms of H. pylori urease. The direct comparison between different isotype and molecular forms, but of unique specificity, demonstrates that SIgA and IgAp/d are more efficient in blocking free and H. pylori-associated urease than IgG and scFv. We conclude that the expression system reported herein will represent a valuable tool to produce human SIgA Ab of multiple specificities against H. pylori antigens involved in colonization and persistence.
Berdoz
José
J
Galli-Valerio Institute, Rue César-Roux 37, 1014 Lausanne, Switzerland.
Corthésy
Blaise
B
D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D013997:Time Factors; D014510:Urease / Q000037:antagonists & inhibitors / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D014510:Urease