Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding.

Abstract

Oral immunization of an animal is generally hard to achieve unless large quantities of antigen are administered. In this study a number of antigens were tested for their ability to elicit a systemic immune response upon oral administration. It was found that bacterial pili, LTB, lectins, and a viral hemagglutinin were all able to elicit significant antibody titers upon oral feeding. The immune response thus generated to LTB and K99 pili could be completely abolished by cofeeding a number of sugars that have close structural homology to the terminal sugars of the GM1 and GM2 gangliosides to which these molecules are known to bind. All of the proteins that were active in oral immunization are known to possess "lectin or lectin-like" binding activities. It is therefore proposed that these molecules are able to bind to glycolipids and glycoproteins on the intestinal mucosa and to stimulate these cells to transport the proteins into the systemic circulation, thereby eliciting a systemic immune response. Molecules that did not possess this binding activity were unable to elicit significant responses at the doses tested.

Effects of different routes of administration on the immunogenicity of the Tat protein and a Tat-derived peptide

“…Indeed, some studies have shown that the oral administration of antigens capable of binding to mucosal surface induces strong immune responses. 36 In fact, Tat has been reported to bind to heparan sulfate proteoglycans present in the extracellular matrix and on the cell membranes 37,38 as well as to integrins present on the cellular surface of professional antigen presenting cells. 39 However, some issues still need to be solved in the field of mucosal vaccines.…”

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

“…These molecules possess a modular organization with at least one noncatalytic domain that reversibly binds to a specific mono-or oligosaccharide (47,48). For example, the most powerful mucosal antigens/adjuvants identified to date, cholera toxin (CT) secreted by Vibrio cholerae and Escherichia coli heat-labile enterotoxin (LT), feature a lectin-like structure with five modules (B subunit) that bind to oligosaccharide residues on membrane receptors (1,46). In keeping with this view, it has recently been reported that plant lectins, also showing a modular structure, such as mistletoe and Lycospersicum esculentum lectins, are potent mucosal immunogens and enhance the immune response to coadministered antigens (25,50).…”

Immune response induced in mice oral immunization with cowpea severe mosaic virus

“…Indeed, the experiments carried out with recombinant viral particles also did not mention specific IgE synthesis (1,11). Furthermore, previous studies using oral immunizations have reported sensitization of IgE suppressor cells (29) with concomitant suppression of serum IgE response due to tolerance induced by oral feeding with proteins (37).…”

“…Thus, the immunogenicity of the CPSMV capsid proteins could be attributed to their "lectin-like" binding activities, which are comparable to similar activities found in bacterial pili, lectins, cholera labile toxin B subunit, and viral hemagglutinin. These are all known to bind to the glycolipids or glycoproteins of the intestinal mucosa cells, thus stimulating these cells to transport the antigen into the systemic circulation (29)(30)(31)(32)(33).…”