The TLR4 agonist adjuvant SLA-SE promotes functional mucosal antibodies against a parenterally delivered ETEC vaccine

Many pathogens establish infection at mucosal surfaces such as the enteric pathogen Enterotoxigenic E. coli (ETEC). Thus, there is a pressing need for effective vaccination strategies that promote protective immunity at mucosal surfaces. Toll-like receptor (TLR) ligands have been extensively developed as vaccine adjuvants to promote systemic immunity, whereas attenuated bacterial toxins including cholera toxin and heat-labile toxin (LT) have initially been developed to promote mucosal immunity. Here we evaluate the ability of the TLR4 agonist second-generation lipid adjuvant formulated in a stable emulsion (SLA-SE) to augment functional mucosal antibodies elicited by intramuscular immunization with a recombinant ETEC vaccine antigen. We find that, in mice, parenterally delivered SLA-SE is at least as effective as the double-mutant LT (LTR192G/L211A, dmLT) adjuvant in promoting functional antibodies and eliciting intestinal IgA responses to the vaccine antigen. In addition, SLA-SE enhanced both the IgG2a response in the mucosa and serum, and the production of LT neutralizing serum antibodies elicited by dmLT four to eightfold. These results reveal unexpected mucosal adjuvant properties of this TLR4 agonist adjuvant when delivered intramuscularly. This may have a substantial impact on the development of vaccines against enteric and other mucosal pathogens.
Mucosal immunity: parenteral vaccination hits the gut Although offering great potential for generating intestinal immunity, vaccination by the oral route suffers from several barriers such as the breakdown of protein vaccines in the stomach and/or the induction of oral tolerance. To investigate whether these barriers can be circumvented, Mark T. Orr and colleagues at the Infectious Disease Research Institute use a parenteral (intramuscular) vaccination protocol in mice. Intramuscular immunization with an enterotoxigenic E. coli (ETEC) vaccine plus a Toll-like receptor 4 adjuvant in stable emulsion (SLA-SE) elicits a functional antibody response in both the gut and serum. Importantly, this intramuscular vaccination triggers robust production of IgA in the gut. These findings suggest that with the right adjuvant combination it might possible to generate potent protective mucosal immunity following parenteral immunization.