Protection of rat intestine against cholera toxin challenge by monoclonal anti-idiotypic antibody immunization via enteral and parenteral routes

Abstract

A mouse monoclonal anti-idiotypic (anti-id) immunoglobulin M (IgM) antibody, called MAb2, was raised against a mouse monoclonal anti-cholera toxin (anti-CT) antibody (MAbl). The MAb2 was shown, by competition with CT for MAbl, to bear the internal image of an epitope of CT. MAb2 immunization of rats was performed via the intraperitoneal, intragastric, and intrajejunal routes and compared with immunization of rats with either a control, isotype-and allotype-matched MAb or with CT via the same routes. Both serum IgG and bile IgA anti-CT Ab3's were detected by enzyme-linked immunosorbent assay in anti-id MAb2immunized rats, although their titers were lower than those in CT-immunized rats. No anti-CT antibodies were detected in sera and bile of rats immunized with the control MAb. When tested for degree of gut protection against a CT challenge, rats immunized with MAb2 by the intrajejunal route showed a rather high degree of protection, which was only slightly lower than that of rats immunized with CT via the same route; all rats but one immunized with the control MAb were unprotected. There was, however, no correlation between serum or bile anti-CT titers and degree of gut protection in MAb2-immunized rats. Their serum anti-CT Ab3's were purified by adsorption and elution from a CT immunosorbent and resembled anti-CT MAbl in their unique reactivity with MAb2. This constitutes to our knowledge the second report of protection against a pathogen by anti-id immunization via the enteric route.

The Transfer of Immunity from Mother to Child

“…21 In experimental systems such anti-idiotypic antibodies delivered orally could induce active protection. 46 The possible effect of monoclonal anti-idiotypic antibodies from mouse against the E. coli K13 polysaccharide over two subsequent generations when given orally was studied in neonatal rats. 47 Two-day-old pups were tube-fed with either 1 or 10 µg of IgG1 antiidiotypic anti-K13.…”

Characterization of an anti-idiotypic MoAb bearing an internal image of the receptor-binding epitope of cholera toxin

“…The anti-CT mAbl [27] used to produce anti-idiotypic mAb2, as described [26], was an IgG 1 (1G4), specific for the B subunit of CT (CT-B), This mAbl competed with CT for binding to GM 1, as demonstrated both by ELISA and latex (Lx) agglutination immunoassay [27]. Another anti-CT IgG I mAbl (3B3) had the same apparent specificity as 1G4.…”

“…called mAb2, was purified on a mAbl (IG4}-Sepharose immunoadsorbent (lads), as described below. A control IgM anti-idiotypic MoAb, called control mAb2 (Co-mAb2), was raised against another anti-CT mAbl (4C5) [26]. mAb2 and Co-mAb2 each mimicked a different CT-B epitope.…”

“…An irrelevant anti-lipopolysaccharide (LPS) MoAb [28]. as well as normal polyclonal mouse IgG and IgM [26], and polyclonal mouse anti-CT antibodies [29], were used as controls and/or lads, as appropriate.…”

“…Anti-idiotypic antibodies are also useful to search for a pathogenic role of anti-receptor antibodies in autoimmune diseases [18,19], [2tX) Brussels, Belgium, sitic [22] and bacterial [23,24] infections. We partly succeeded [25,26] in protecting rats against an intestinal CT-challenge by anti-idiotype vaccination. Here, we characterize a new mouse anti-idiotypic MoAb, mAb2, that mimics a receptor-binding epitope of CT and elicits anti-CT antibodies, Ab3, after injections into rabbits.…”