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.

许多病原体会在粘膜表面形成感染，例如肠病原体Enterotoxigenic E. coli（ETEC）。因此，迫切需要有效的疫苗接种策略以促进粘膜表面的保护性免疫。Toll样受体（TLR）配体已被广泛用作疫苗佐剂，以促进全身免疫，而减毒细菌毒素，包括霍乱毒素和不耐热毒素（LT），最初已被开发以促进粘膜免疫。在这里，我们评估了稳定乳液（SLA-SE）中配制的TLR4激动剂第二代脂质佐剂增强通过重组ETEC疫苗抗原进行肌肉内免疫引发的功能性粘膜抗体的能力。我们发现，在小鼠中，胃肠外递送的SLA-SE至少与双突变型LT（LTR192G / L211A，dmLT）佐剂，可促进功能性抗体并引起肠道IgA对疫苗抗原的应答。另外，SLA-SE增强了粘膜和血清中的IgG2a反应，并通过dmLT引起的中和血清抗体的产生提高了4到8倍。这些结果揭示了当肌肉内递送时该TLR4激动剂佐剂的出乎意料的粘膜佐剂性质。这可能对开发针对肠道和其他粘膜病原体的疫苗产生重大影响。