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

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• 作者：Jeroen Geurtsen ; Floris Fransen ; Rob J. V ; ebriel ; Eric R. Gremmer ; Liset J.J. de la Fonteyne-Blankestijn ; Betsy Kuipers ; Jan Tommassen ; Peter van der Ley
• 关键词：Bordetella pertussis ; Whole-cell pertussis vaccines ; Lipopolysaccharide ; LpxL2 ; Monophosphoryl lipid A
• 刊名：Vaccine
• 出版年：2008
• 出版时间：13 February 2008
• 年：2008
• 卷：26
• 期：7
• 页码：899-906
• 全文大小：449 K

文摘

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.