Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1996-11-20
|
| pubmed:abstractText |
To evaluate the host immune response to long-term repeat administration of adenovirus vector, rhesus monkeys were treated at intervals of approximately 3 weeks with up to 18 instillations of Ad2/CFTR-2, a second generation vector encoding the cystic fibrosis transmembrane conductance regulator (CFTR). All monkeys instilled with Ad2/CFTR-2 developed a significant humoral immune response against adenovirus but not CFTR. Antibodies with virus neutralizing activity were detected in the serum and bronchoalveolar lavage (BAL) of all vector-treated monkeys and included both IgG and secretory IgA. Virus-specific T cells capable of proliferating in response to stimulation with adenovirus antigen were detected in all vector-treated monkeys. No CFTR-specific proliferation of peripheral blood lymphocytes was detected. An increase in the proportion of CD8+ T cells was noted in the BAL of virus-treated monkeys but cells from the BAL displayed little or no cytolytic activity against infected autologous fibroblasts when tested under a variety of culture conditions. However, MHC-restricted cytolytic activity was detected in the tracheobronchial lymph nodes and spleen of one of three virus-treated monkeys tested. MHC-unrestricted killing of infected fibroblasts was also observed with spleen cells from all animals tested. From these results, it appears that both the humoral and cell-mediated arms of the immune response were stimulated by repeated administration of high doses of Ad2/CFTR-2 suggesting that effective, long-term adenovirus gene therapy may require modification of the vector or treatment of the host to allow the virus to evade host immune defenses.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0969-7128
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
3
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
117-27
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8867859-Adenoviruses, Human,
pubmed-meshheading:8867859-Animals,
pubmed-meshheading:8867859-Antibodies, Viral,
pubmed-meshheading:8867859-Antigens, CD,
pubmed-meshheading:8867859-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:8867859-Cystic Fibrosis,
pubmed-meshheading:8867859-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:8867859-Cytotoxicity, Immunologic,
pubmed-meshheading:8867859-Dose-Response Relationship, Drug,
pubmed-meshheading:8867859-Gene Therapy,
pubmed-meshheading:8867859-Genetic Vectors,
pubmed-meshheading:8867859-Immunoglobulin A,
pubmed-meshheading:8867859-Lymph Nodes,
pubmed-meshheading:8867859-Lymphocyte Activation,
pubmed-meshheading:8867859-Macaca mulatta,
pubmed-meshheading:8867859-Neutralization Tests,
pubmed-meshheading:8867859-Spleen,
pubmed-meshheading:8867859-T-Lymphocytes
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Humoral and cellular immune responses of nonhuman primates to long-term repeated lung exposure to Ad2/CFTR-2.
|
| pubmed:affiliation |
Genzyme Corporation, Framingham, MA 01701-9322, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|