Liposomes containing anti-idiotypic antibodies: an oral vaccine to induce protective secretory immune responses specific for pathogens of mucosal surfaces

Abstract

By using a gnotobiotic rat model system to study the induction of protective immune responses by anti-idiotype (anti-id) vaccines specific for antibodies directed at the cariogenic microorganism Streptococcus mutans, it was shown that administration of such an anti-id vaccine provided partial protection against dental caries after challenge with virulent microorganisms. Protective effects were first demonstrated by direct parenteral administration of the anti-id vaccine into salivary gland regions, as determined by reductions in microbial colonization and caries scores. Subsequently, the anti-id was incorporated into liposomes and administered by gastric intubation. Immunization by this regimen also resulted in a significant reduction in caries as well as S. mutans colonization of the oral cavity, with concomitant increases in salivary immunoglobulin A anti-S. mutans antibodies. These data provide evidence that anti-id vaccines specifically targeted at the secretory immune system can induce protective immune responses to pathogens of mucosal surfaces.

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

“…immunizations. Recently (11), Abs against Streptococcus mutans and some degree of protection against caries induced by this pathogen were obtained in germfree rats after repeated parenteral (intrasalivary gland) or enteral (i.g.) injections of polyclonal rabbit anti-rat-id affinity-purified Abs; in the case of the i.g.…”

“…Such studies are now under way in our group (39), as well as studies of various amounts of MAb2, their liposomal entrapment, and their anti-CT priming potential and/or memoryevoking capacity. The anti-caries anti-id immunization by Jackson et al (11) was the first published attempt at anti-id vaccination by stimulation of the intestinal immune system, obviously a major concern since mucosae are the natural port of entry of most pathogens. However, in that study (11), in which some protection was provided by the antistreptococcal anti-id vaccine, some ambiguity remained, because the challenge with the cariogenic streptococci, necessary to measure the protection, was done well before completion of the anti-id vaccine administrations, and this infection, therefore, could have induced some boosterlike effect in the anti-id vaccineprimed animals and/or could have primed the animals for subsequent anti-id vaccine responses.…”

“…The anti-caries anti-id immunization by Jackson et al (11) was the first published attempt at anti-id vaccination by stimulation of the intestinal immune system, obviously a major concern since mucosae are the natural port of entry of most pathogens. However, in that study (11), in which some protection was provided by the antistreptococcal anti-id vaccine, some ambiguity remained, because the challenge with the cariogenic streptococci, necessary to measure the protection, was done well before completion of the anti-id vaccine administrations, and this infection, therefore, could have induced some boosterlike effect in the anti-id vaccineprimed animals and/or could have primed the animals for subsequent anti-id vaccine responses. Another difference between the anti-id caries immunization (11) and our present data is the fact that both the rat antistreptococcal id Abs and the corresponding rabbit anti-id Abs were polyclonal and hence much more complex and less characterized, whereas both our id MAbl and anti-id MAb2 were well-defined MAbs.…”

Effectiveness of Liposomes Possessing Surface-Linked Recombinant B Subunit of Cholera Toxin as an Oral Antigen Delivery System

“…Liposomes are bilayered phospholipid membrane vesicles that have attracted considerable interest as mucosal delivery systems (8,14,21,24,26). Following oral administration, the portal of liposome entry into the gut-associated lymphoid tissue (GALT) is believed to be via the M cells of the Peyer's patches.…”

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

“…Sueh uses have been explored in the reovirus type 3 anti-idiotype system [16,17]. 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.…”