Linked Life Data

14517067

Source:http://linkedlifedata.com/resource/pubmed/id/14517067

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-9-30
pubmed:abstractText
HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector-borne immunogens.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
134-46
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14517067-AIDS Vaccines, pubmed-meshheading:14517067-Animals, pubmed-meshheading:14517067-Cytokines, pubmed-meshheading:14517067-Cytotoxicity Tests, Immunologic, pubmed-meshheading:14517067-Enhancer Elements, Genetic, pubmed-meshheading:14517067-Female, pubmed-meshheading:14517067-Gene Products, rev, pubmed-meshheading:14517067-HIV Antibodies, pubmed-meshheading:14517067-HIV Envelope Protein gp160, pubmed-meshheading:14517067-HIV Infections, pubmed-meshheading:14517067-HIV-1, pubmed-meshheading:14517067-Humans, pubmed-meshheading:14517067-Lymphocyte Activation, pubmed-meshheading:14517067-Mason-Pfizer monkey virus, pubmed-meshheading:14517067-Mice, pubmed-meshheading:14517067-Mice, Inbred BALB C, pubmed-meshheading:14517067-Plasmids, pubmed-meshheading:14517067-T-Lymphocytes, pubmed-meshheading:14517067-T-Lymphocytes, Cytotoxic, pubmed-meshheading:14517067-Vaccines, DNA, pubmed-meshheading:14517067-rev Gene Products, Human Immunodeficiency Virus
pubmed:year
2003
pubmed:articleTitle
Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't