THE ROLE OF ADP-RIBOSYLATION AND G(M1)-BINDING ACTIVITY IN THE MUCOSAL IMMUNOGENICITY AND ADJUVANTICITY OF THE ESCHERICHIA-COLI HEAT-LABILEENTEROTOXIN AND VIBRIO-CHOLERAE CHOLERA-TOXIN
L. Dehaan et al., THE ROLE OF ADP-RIBOSYLATION AND G(M1)-BINDING ACTIVITY IN THE MUCOSAL IMMUNOGENICITY AND ADJUVANTICITY OF THE ESCHERICHIA-COLI HEAT-LABILEENTEROTOXIN AND VIBRIO-CHOLERAE CHOLERA-TOXIN, Immunology and cell biology, 76(3), 1998, pp. 270-279
The mucosal route of vaccination has attracted a great deal of attenti
on recently. Not only is mucosal application of vaccines, for example,
orally or intranasally, particularly convenient, it also offers the p
ossibility to induce locally produced and secreted S-IgA antibodies in
addition to systemic IgG antibodies. These IgA antibodies are known t
o play a key role in protection against pathogens that invade the host
through mucosal surfaces. Induction of such responses is not readily
achieved by currently used vaccination strategies, which generally inv
olve intramuscular or subcutaneous injection with inactivated pathogen
s or antigens thereof. For the induction of a mucosal immune response,
the vaccine needs to be applied locally. However, local vaccination w
ith non-replicating antigens is usually ineffective and may result in
tolerance unless a mucosal immunoadjuvant is included. The most potent
mucosal immunoadjuvants known to date are probably cholera toxin (CT)
and the closely related Escherichia coli heat-labile enterotoxin (LT)
. Although CT and LT have become standard adjuvants for experimental m
ucosal vaccines, the intrinsic toxicity has thus far precluded their u
se as adjuvants for human vaccine formulations. In the present review,
the mucosal immunogenic and adjuvant properties of LT and CT are desc
ribed, with special emphasis on the functional role of the individual
subunits on their immune-stimulatory properties.