Title
Human CD46-transgenic mice in studies involving replication-incompetent adenoviral type 35 vectors
Author
Verhaagh, S.
de Jong, E.
Goudsmit, J.
Lecollinet, S.
Gillissen, G.
de Vries, M.
van Leuven, K.
Que, I.
Ouwehand, K.
Mintardjo, R.
Weverling, G.J.
Radošević, K.
Richardson, J.
Eloit, M.
Lowik, C.
Quax, P.
Havenga, M.
TNO Kwaliteit van Leven
Publication year
2006
Abstract
Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here, it is reported that CD46 transgenic mice (MYII-strain) express CD46 in all major organs and that it functions as a receptor for rAd35 vectors. Similar to monkeys and humans, MYII mice highly express CD46 in their lungs and kidneys and demonstrate low expression in muscle. Upon intravenous administration, rAd35 vector genomes as well as expression are detected in lungs of MYII mice, in contrast to wild-type littermates. Expression was predominantly detected in lung epithelial cells. Upon intramuscular administration, the initial level of luciferase expression is higher in MYII mice as compared with wild-type littermates, in spite of the fact that CD46 expression is low in muscle of MYII mice. The higher level of expression in muscle of MYII mice results in prolonged gene expression as assessed by CCD camera imaging for luciferase activity. Finally, a significant dose-sparing effect in MYII mice as compared with wild-type littermates on anti-SIVgag CD8+ T-cell induction following intramuscular vaccination with an rA35.SIVgag vaccine was observed. This dose-sparing effect was also observed when reinfusing dendritic cells derived from MYII mice after exposure to rAd35.SIVgag vaccine as compared with rAd35.SIVgag exposed dendritic cells from wild-type littermates. It was concluded that MYII mice represent an interesting preclinical model to evaluate potency and safety of rAd35 vectors. © 2006 SGM. Chemicals / CAS: Antigens, CD46
Subject
Biology
Biomedical Research
Adenovirus vector
Beta galactosidase
CD8 antigen
Gag protein
Luciferase
Membrane cofactor protein
Simian immunodeficiency virus vaccine
Animal cell
Animal experiment
Antigen expression
Antigen function
Camera
CD8+ T lymphocyte
Cellular immunity
Controlled study
Dendritic cell
Drug potency
Drug safety
Female
Gene expression
Human adenovirus
Imaging system
Kidney cell
Lung alveolus epithelium
Male
Mouse
Mouse strain
Muscle cell
Nonhuman
Receptor affinity
Transgenic mouse
Viral gene delivery system
Virus replication
Wild type
Adenoviruses, Human
Animals
Antigens, CD46
Genetic Vectors
Humans
Mice
Mice, Transgenic
Virus Replication
Adenoviridae
Animalia
Human adenovirus
Mus musculus
Simian immunodeficiency virus
To reference this document use:
http://resolver.tudelft.nl/uuid:af88071f-a1c4-4ef8-8050-3f1aff402b73
DOI
https://doi.org/10.1099/vir.0.81293-0
TNO identifier
239103
ISSN
0022-1317
Source
Journal of General Virology, 87 (2), 255-265
Document type
article