Linked Life Data

8108420

Source:http://linkedlifedata.com/resource/pubmed/id/8108420

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-3-22
pubmed:abstractText
Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), were evaluated for therapeutic efficacy in infected mice just before or at the time of peak virus replication in the lungs. Fab 19, which neutralized RSV infectivity with high efficiency in tissue culture, was effective therapeutically when delivered directly into the lungs by intranasal instillation under anesthesia. In contrast, RSV Fab 126, which failed to neutralize virus in cell culture, did not exhibit a therapeutic effect under these conditions. The amount of Fab 19 required to effect a 5000- to 12,000-fold reduction in titer of RSV in the lungs within 24 hr was rather small. In four separate experiments, a single instillation of 12.9-50 micrograms of RSV Fab 19 was sufficient to achieve such a reduction in pulmonary virus in a 25g mouse. The use of Fabs instead of the whole immunoglobulin molecules from which they are derived reduced the protein content of a therapeutic dose. This is important because the protein load that can be delivered effectively into the lungs is limited. The therapeutic effect of a single treatment with Fab 19 was not sustained, so that a rebound in pulmonary virus titer occurred on the 2nd day after treatment. This rebound in pulmonary RSV titer could be prevented by treating infected mice with a single dose of Fab 19 daily for 3 days. These observations suggest that human monoclonal Fabs grown in Escherichia coli may prove useful in the treatment of serious RSV disease as well as diseases caused by other viruses where replication in vivo is limited primarily to the lumenal lining of the respiratory tract.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-1279672, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-1384050, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-1719545, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-1896445, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-2186179, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-2251875, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-3439796, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-3553614, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-362946, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-3907188, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-5933417, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-8354080, http://linkedlifedata.com/resource/pubmed/commentcorrection/8108420-8413475
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1386-90
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fab is effective therapeutically when introduced directly into the lungs of RSV-infected mice.
pubmed:affiliation
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't