Lipopolysaccharide (LPS), a dominant component of the Gram-negative bacterial outer membrane, is a strong activator of the innate immune system, and thereby an important determinant in the adaptive immune response following bacterial infection. This adjuvant activity can be harnessed following immunization with bacteria-derived vaccines that naturally contain LPS, and when LPS or molecules derived from it are added to purified vaccine antigens. However, the downside of the strong biological activity of LPS is its ability to contribute to vaccine reactogenicity. Modification of the LPS structure allows triggering of a proper immune response needed in a vaccine against a particular pathogen while at the same time lowering its toxicity. Extensive modifications to the basic structure are possible by using our current knowledge of bacterial genes involved in LPS biosynthesis and modification. This review focuses on biosynthetic engineering of the structure of LPS and implications of these modifications for generation of safe adjuvants.
Keywords: TLR4; adjuvant; lipid A; lipopolysaccharide; oligosaccharide; outer membrane vesicle; pathogenic bacteria; vaccine.