Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2005-11-24
pubmed:abstractText
Molecularly defined vaccine formulations capable of inducing antiviral CD8+ T-cell-specific immunity in a manner compatible with human delivery are limited. Few molecules achieve this target without the support of an appropriate immunological adjuvant. In this study, we investigate the potential of totally synthetic palmitoyl-tailed helper-cytotoxic-T-lymphocyte chimeric epitopes (Th-CTL chimeric lipopeptides) to induce herpes simplex virus type 1 (HSV-1)-specific CD8+ T-cell responses. As a model antigen, the HSV-1 glycoprotein B498-505 (gB498-505) CD8+ CTL epitope was synthesized in line with the Pan DR peptide (PADRE), a universal CD4+ Th epitope. The peptide backbone, composed solely of both epitopes, was extended by N-terminal attachment of one (PAM-Th-CTL), two [(PAM)2-Th-CTL], or three [(PAM)3-Th-CTL] palmitoyl lysines and delivered to H2b mice in adjuvant-free saline. Potent HSV-1 gB498-505-specific antiviral CD8+ T-cell effector type 1 responses were induced by each of the palmitoyl-tailed Th-CTL chimeric epitopes, irrespective of the number of lipid moieties. The palmitoyl-tailed Th-CTL chimeric epitopes provoked cell surface expression of major histocompatibility complex and costimulatory molecules and production of interleukin-12 and tumor necrosis factor alpha proinflammatory cytokines by immature dendritic cells. Following ocular HSV-1 challenge, palmitoyl-tailed Th-CTL-immunized mice exhibited a decrease of virus replication in the eye and in the local trigeminal ganglion and reduced herpetic blepharitis and corneal scarring. The rational of the molecularly defined vaccine approach presented in this study may be applied to ocular herpes and other viral infections in humans, providing steps are taken to include appropriate Th and CTL epitopes and lipid groups.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-10075159, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-10566149, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-10623838, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-10799875, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-10812228, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-10980387, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11009315, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11123327, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11426068, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11595295, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11739679, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11851314, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11851327, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-11972639, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12127354, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12209640, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12391202, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12525427, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12643762, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12767989, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12787761, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12895273, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-12915561, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-14512570, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-14744892, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15099562, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15102368, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15140061, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15233729, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15256473, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15489266, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-15603887, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-1847447, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-2153234, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-7677961, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-9174617, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-9449714, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-9480978, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-9722921, http://linkedlifedata.com/resource/pubmed/commentcorrection/16306600-9811690
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-538X
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15289-301
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Th-cytotoxic T-lymphocyte chimeric epitopes extended by Nepsilon-palmitoyl lysines induce herpes simplex virus type 1-specific effector CD8+ Tc1 responses and protect against ocular infection.
pubmed:affiliation
Laboratory of Cellular and Molecular Immunology, University of California, Irvine, College of Medicine, Bldg. 55, Room 202, Orange, CA 92868, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural