Bacterial lipopolysaccharide as adjuvants

Abstract

Lipopolysaccharide (LPS, endotoxin) is a major component of the outer membrane of gram negative bacteria. It is an activator of humoral and cellular responses in humans with potential use as adjuvant in vaccine technology. Importantly, LPS has a large capacity to induce Th1-type responses and stimulate cytotoxic T lymphocytes, which are poorly obtained by standard adjuvants but required for specific immune stimulatory therapies. In contrast, LPS possess an extreme toxicity that limit its clinical use in humans. Alteration of its chemical structure led the generation of LPS-based derivatives with reduced toxicity but retaining adjuvant properties. Monophosphoryl lipid A (MPLA) has been the most successful LPS-based adjuvant, currently incorporated in approved vaccine preparations and extensively used in vaccine trials and preclinical studies. Novel designed structures, analogous to LPS and generated by chemical synthesis, can offer lower production cost and lesser heterogenic formulations than MPLA and, in addition, be even most suitable for specific immune therapies. Thus, LPS-based structures are valuable contributions as adjuvants in human vaccinology and open new possibilities to existing demands for specific therapies.