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Vaccine. 2008 Feb 13;26(7):899-906. doi: 10.1016/j.vaccine.2007.12.012. Epub 2007 Dec 31.

Supplementation of whole-cell pertussis vaccines with lipopolysaccharide analogs: modification of vaccine-induced immune responses.

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Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands.


Lipopolysaccharide (LPS) is one of the main constituents of the Gram-negative bacterial outer membrane. Besides being an endotoxin, LPS also possesses a powerful adjuvant activity. Previously, it has been shown that changes in the chemical composition of the lipid A domain of LPS modulate its biological activity. For example, monophosphoryl lipid A (MPL) has been shown to be a non-toxic immunostimulatory compound. Moreover, several LPS analogs have been shown to antagonise LPS-induced signalling in eukaryotic cells. In the present study, we show that supplementation of a whole-cell pertussis (wP) vaccine with LPS analogs modulates the vaccine-induced immune responses. We show in a mouse-model system that addition of MPL to a wP vaccine increases vaccine efficacy without altering vaccine-induced serum pro-inflammatory cytokine levels. Furthermore, we show that Neisseria meningitidis LpxL2 LPS, an LPS species derived from a N. meningitidis lpxL2 mutant, antagonises wP and LPS-stimulated interleukin-6 (IL-6) production by macrophages in vitro, and that addition of this LPS-derivative to the wP vaccine decreases vaccine-induced serum IL-6 levels and increases vaccine efficacy.

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