Structure of the sugar-phosphate moiety of lipid A from lipooligosaccharide of Neisseria meningitidis group B, strain BC5S No. 125

1992 ◽  
Vol 157 (2) ◽  
pp. 131-134 ◽  
Author(s):  
Vyacheslav L. L'vov ◽  
Irina K. Verner ◽  
Larisa Yu. Musina ◽  
Alexander V. Rodionov ◽  
Anatoly V. Ignatenko ◽  
...  
2009 ◽  
Vol 17 (1) ◽  
pp. 98-107 ◽  
Author(s):  
Mark B. Stoddard ◽  
Valerian Pinto ◽  
Paul B. Keiser ◽  
Wendell Zollinger

ABSTRACT Bacterial endotoxin interacts with the human immune system via complex immunological pathways. The evaluation of endotoxicity is important in the development of safe vaccines and immunomodulatory therapeutics. The Limulus amebocyte lysate (LAL) assay is generally accepted by the FDA for use for the quantification of lipopolysaccharide (LPS), while the rabbit pyrogen test (RPT) is used to estimate pyrogenicity during early development and production. Other in vitro assays, such as cytokine release assays with human whole blood (WB) or peripheral blood mononuclear cells (PBMCs), have also been used and may better estimate the human immunological response to products containing novel LPS molecules. In this study, WB and PBMC interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) release assays were used to estimate the endotoxic activities of purified LPS and native outer membrane vesicle (NOMV) vaccines derived from wild-type (hexa-acylated lipid A) and genetically detoxified (penta- and tetra-acylated lipid A) group B Neisseria meningitidis. A method for quantification of the differences in endotoxicity observed in the WB and PBMC assays is elucidated. The LAL assay was shown to be relatively insensitive to lipid A variations, and the RPT was less sensitive than the cytokine release assay with WB. The IL-6 and TNF-α assays with WB but not the assays with PBMCs distinguished between vaccines containing LPS from penta- and tetra-acylated strains. The high degree of sensitivity of the WB system to LPS variations and the presumed relevance of the use of human tissues to predict toxicity in humans suggest that this assay may be particularly well suited for the safety evaluation of vaccines and therapeutics containing acylation variants of LPS.


Vaccine ◽  
2006 ◽  
Vol 24 (26) ◽  
pp. 5420-5425 ◽  
Author(s):  
Duzhang Zhu ◽  
Vicki Barniak ◽  
Ying Zhang ◽  
Bruce Green ◽  
Gary Zlotnick

1992 ◽  
Vol 6 (23) ◽  
pp. 3493-3499 ◽  
Author(s):  
Gerardo A. Zapata ◽  
Willie F. Vann ◽  
Yaffa Rubinstein ◽  
Carl E. Frasch

2019 ◽  
Vol Volume 12 ◽  
pp. 3169-3188 ◽  
Author(s):  
Irene Rivero-Calle ◽  
Peter Francis Raguindin ◽  
Jose Gómez-Rial ◽  
Carmen Rodriguez-Tenreiro ◽  
Federico Martinón-Torres

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amaka M. Awanye ◽  
Chun-Mien Chang ◽  
Jun X. Wheeler ◽  
Hannah Chan ◽  
Leanne Marsay ◽  
...  

1991 ◽  
Vol 106 (3) ◽  
pp. 445-457 ◽  
Author(s):  
S. F. Olsen ◽  
B. Djurhuus ◽  
K. Rasmussen ◽  
H. D. Joensen ◽  
S. O. Larsen ◽  
...  

SUMMARYIn a household survey in the Faroe Islands, an isolated community with hyperendemic occurrence of meningococcal disease due to serogroup B 15, 1604 persons were examined for pharyngeal carriage of Neisseria meningitidis and N. lactamica. Two areas were chosen having experienced high (HIA), and two having experienced low incidences (LIA) of disease. Living in HIA compared with LIA was associated with higher risk of N. meningitidis B 15 carriage and lower risk of N. lactamica carriage, with odds ratios of 2·7 (95% confidence interval (CI) 1·4–5·1, P = 0·003) and 0·41 (95% CI 0·31–0·53, P < 0·0001), respectively. In HIA the risk of N. meningitidis carriage was much lower in non-carriers than carriers of N. lactamica, with an odds ratio of 0·19 (95% CI 0·08–0·47, P = 0·0003); in LIA this association (odds ratio 0·51, P = 0·05) was much weaker. Children 0–14 years had substantially higher risk of being carriers of N. meningitidis group B 15 if the mothers were so, with an odds ratio of 11 (95% CI 4–29, P < 0·0001).


2008 ◽  
Vol 76 (8) ◽  
pp. 3801-3807 ◽  
Author(s):  
Liana Steeghs ◽  
A. Marijke Keestra ◽  
Andries van Mourik ◽  
Heli Uronen-Hansson ◽  
Peter van der Ley ◽  
...  

ABSTRACT Neisseria meningitidis LpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in future N. meningitidis vaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties. Unexpectedly, purified LpxL1 LPS displayed minimal human DC-stimulating properties compared to wild-type LPS. Although whole bacteria induced DC maturation and activation irrespective of their type of LPS, the LpxL1 mutant failed to activate the human recombinant TLR4/MD-2 complex expressed in HeLa cells. Similarly, purified LpxL1 LPS was unable to activate human TLR4/MD-2 and it even acted as an antagonist of wild-type LPS. Both wild-type and LpxL1 LPSs activated the murine TLR4/MD-2 complex, consistent with their abilities to induce maturation and activation of murine DC. Assays with cells transfected with different combinations of human and murine TLR4 and MD-2 indicated that TLR4 was a more-major determinant of the LPS response than MD-2. The species-specific activation of the TLR4/MD-2 complex by LpxL1 LPS may have an impact on the use of LpxL1 LPS as an adjuvant and the use of murine immunization models in human meningococcal vaccine development.


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