Adenovirus fibre exchange alters cell tropism in vitro but not transgene-specific T CD8+ immune responses in vivo.
Gene transfer with recombinant adenoviruses (rAds) is a powerful means of inducing an immune response against a transgene product. However, little is known about the mechanisms that underlie the induction of the immune response after intramuscular inoculation of adenovirus and, in particular, the relative role of the different cell types transduced. Several studies have suggested that CD8+ cytotoxic T lymphocyte responses elicited after inoculation of adenoviruses (Ads) are induced both by direct transduction of antigen presenting cells (APCs) and by cross-priming. In the present study, a library of fibre-chimeric rAds was screened in order to identify rAds with distinct capacities to express transgene product in murine cell types naturally found in muscle, i.e. myoblasts, endothelial cells (both representing non-APCs) and dendritic cells (representing APCs). Four selected pseudotypes, differing in their ability to infect muscular cells were used to immunize C57BL/6 mice. The relationship between the capacity to transduce non-APC or APC in vitro and the ability to induce humoral and cellular responses against the beta-galactosidase antigen after intramuscular inoculation were studied. Results indicate that CD8+ T cell responses against the beta-galactosidase antigen were similar after inoculation of the four viruses, thus revealing no direct relationship with their ability to transduce myoblasts, endothelial cells or dendritic cells in vitro.
Mercier
S
S
UMR INRA-AFSSA-ENVA 1161, Virologie, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort Cedex, France.
Verhaagh
S
S
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.
Goudsmit
J
J
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.
Lemckert
A
A
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.
Monteil
M
M
UMR INRA-AFSSA-ENVA 1161, Virologie, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort Cedex, France.
Havenga
M
M
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.
Eloit
M
M
UMR INRA-AFSSA-ENVA 1161, Virologie, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort Cedex, France.
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D032446:Myoblasts / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D018523:Tropism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000276:immunology
D014764:Viral Proteins; D007371:Interferon-gamma; D001616:beta-Galactosidase