Linked Life Data

15040932

Source:http://linkedlifedata.com/resource/pubmed/id/15040932

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-3-25
pubmed:abstractText
Sepsis continues to be a leading cause of death among hospitalized patients. Despite advances in supportive care and the availability of potent antimicrobials, the mortality exceeds 20%. The passive infusion of antibodies directed against a conserved region of the lipopolysaccharide (LPS) of Gram-negative bacteria was highly protective in an early study (NEJM 307 [1982] 1225). When this and similar preparations were unable to show consistent efficacy, efforts were directed towards other strategies, including cytokine modulation. Our group found that a whole bacterial vaccine made from the Escherichia coli O111:B4, J5 (Rc chemotype) mutant induced protective antibodies when given passively as treatment for sepsis in a neutropenic rat model. A subunit vaccine, composed of detoxified J5 LPS complexed to group B meningococcal outer membrane protein (OMP), provided similar protection when antibodies were given passively, or induced actively in both the neutropenic and cecal ligation/puncture models of sepsis. A phase I study in 24 subjects (at 5, 10 and 25 microg doses [based on LPS] for each group of 8) revealed the vaccine to be well-tolerated with no systemic endotoxin-like effects. Although a two to three-fold increase in antibody levels over baseline (by ELISA assay) was observed at the 10 and 25 microg doses, the plasma from both high and low responders reduced LPS-induced cytokine generation in whole blood. Reimmunization of six subjects at 12 months did not convert low responders to high responders or boost the still elevated anti-J5 LPS levels of high responders. If functional assays of anti-LPS antibodies are better predictors of vaccine efficacy than ELISA antibody levels, then it will be necessary to determine which of many potential assays best correlates with protection in animal models. We are currently comparing a panel of functional assays with protective efficacy in animal models of sepsis, as well as the ability of adjuvants to enhance vaccine efficacy. The availability of an effective anti-endotoxin vaccine will provide additional therapeutic options for the prevention and/or treatment of sepsis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0264-410X
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
812-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Development of an anti-core lipopolysaccharide vaccine for the prevention and treatment of sepsis.
pubmed:affiliation
Department of Medicine, Center for Vaccine Development, University of Maryland, 685 W. Baltimore Street, HSF 480, Baltimore, MD 21201, USA. across@medicine.umaryland.edu
pubmed:publicationType
Journal Article, Review