Linked Life Data

19500523

Source:http://linkedlifedata.com/resource/pubmed/id/19500523

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2009-7-3
pubmed:abstractText
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected approximately two billion individuals worldwide with approximately 9.2 million new cases and 1.6 million deaths annually. Current efforts are focused on making better BCG priming vaccines designed to induce a comprehensive and balanced immunity followed by booster(s) targeting a specific set of relevant antigens in common with the BCG prime. We describe the generation and immunological characterization of recombinant BCG strains with properties associated with lysis of the endosome compartment and over-expression of key Mtb antigens. The endosome lysis strain, a derivative of BCG SSI-1331 (BCG(1331)) expresses a mutant form of perfringolysin O (PfoA(G137Q)), a cytolysin normally secreted by Clostridium perfringens. Integration of the PfoA(G137Q) gene into the BCG genome was accomplished using an allelic exchange plasmid to replace ureC with pfoA(G137Q) under the control of the Ag85B promoter. The resultant BCG construct, designated AERAS-401 (BCG(1331) DeltaureC::OmegapfoA(G137Q)) secreted biologically active Pfo, was well tolerated with a good safety profile in immunocompromised SCID mice. A second rBCG strain, designated AFRO-1, was generated by incorporating an expression plasmid encoding three mycobacterial antigens, Ag85A, Ag85B and TB10.4, into AERAS-401. Compared to the parental BCG strain, vaccination of mice and guinea pigs with AFRO-1 resulted in enhanced immune responses. Mice vaccinated with AFRO-1 and challenged with the hypervirulent Mtb strain HN878 also survived longer than mice vaccinated with the parental BCG. Thus, we have generated improved rBCG vaccine candidates that address many of the shortcomings of the currently licensed BCG vaccine strains.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1873-2518
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4412-23
pubmed:dateRevised
2009-8-20
pubmed:meshHeading
pubmed-meshheading:19500523-Animals, pubmed-meshheading:19500523-Antigens, Bacterial, pubmed-meshheading:19500523-BCG Vaccine, pubmed-meshheading:19500523-Bacterial Toxins, pubmed-meshheading:19500523-Cell Line, pubmed-meshheading:19500523-Erythrocytes, pubmed-meshheading:19500523-Female, pubmed-meshheading:19500523-Genes, Bacterial, pubmed-meshheading:19500523-Guinea Pigs, pubmed-meshheading:19500523-Hemolysin Proteins, pubmed-meshheading:19500523-Hemolysis, pubmed-meshheading:19500523-Immunodominant Epitopes, pubmed-meshheading:19500523-Mice, pubmed-meshheading:19500523-Mice, Inbred BALB C, pubmed-meshheading:19500523-Mice, Inbred C57BL, pubmed-meshheading:19500523-Mice, SCID, pubmed-meshheading:19500523-Mycobacterium bovis, pubmed-meshheading:19500523-Mycobacterium tuberculosis, pubmed-meshheading:19500523-Plasmids, pubmed-meshheading:19500523-Sheep, pubmed-meshheading:19500523-Tuberculosis
pubmed:year
2009
pubmed:articleTitle
Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis.
pubmed:affiliation
Aeras Global TB Vaccine Foundation, 1405 Research Blvd., Rockville, MD 20850, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't