Title
Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: Manufacture on PER.C6 cells, tropism and immunogenicity
Author
TNO Kwaliteit van Leven
Lemckert, A.A.C.
Grimbergen, J.
Smits, S.
Hartkoorn, E.
Holterman, L.
Berkhout, B.
Barouch, D.H.
Vogels, R.
Quax, P.
Goudsmit, J.
Havenga, M.J.E.
Publication year
2006
Abstract
Recombinant adenoviral vectors based on type 5 (rAd5) show great promise as a vaccine carrier. However, neutralizing activity against Ad5 is prevalent and high-titred among human populations, and significantly dampens Ad5-based vaccine modalities. The generation of alternative adenoviral vectors with low seroprevalence thus receives much research attention. Here, it is shown that a member from human adenovirus subgroup D, i.e. Ad49, does not cross-react with Ad5 neutralizing activity, making it a candidate serotype for vector development. Therefore, a plasmid system that allows formation of replication-incompetent adenovirus serotype 49 vaccine vectors (rAd49) was constructed and it was demonstrated that rAd49 can be successfully propagated to high titres on existing Ad5.E1-complementing cell lines such as PER.C6. Using an rAd49 vector carrying the luciferase marker gene, detailed seroprevalence studies were performed, demonstrating that rAd49 has low seroprevalence and neutralizing antibody titres worldwide. Also, we have initiated rAd49 vector receptor usage suggesting that rAd49 utilizes hCD46 as a cellular receptor. Finally, the immunogenicity of the rAd49 vector was assessed and it was shown that an rAd49.SIVGag vaccine induces strong anti-SIVGag CD8+ T-lymphocytes in naive mice, albeit less than an rAd5.SIVGag vaccine. However, in mice with high anti-Ad5 immunity the rAd5.SIVGag vaccine was severely blunted, whereas the anti-SIVGag response was not significantly suppressed using the rAd4g.SIVGag vaccine. These data demonstrate the potential of a replication deficient human group D adenoviral vector for vaccination purposes. © 2006 SGM. Chemicals / CAS: Antibodies, Viral; Antigens, CD46; Vaccines, Synthetic; Viral Vaccines.
Subject
Biomedical Research
adenovirus vector
cell receptor
Gag protein
luciferase
membrane cofactor protein
neutralizing antibody
virus vaccine
adult
aged
animal cell
animal experiment
antibody titer
article
CD8+ T lymphocyte
cell line
controlled study
cross reaction
gene construct
heterozygote
human
Human adenovirus 5
human cell
immunogenicity
marker gene
mouse
nonhuman
nucleotide sequence
plasmid
priority journal
seroprevalence
serotype
Simian immunodeficiency virus
virus replication
Adenoviruses, Human
Animals
Antibodies, Viral
Antigens, CD46
Cell Line
Genetic Engineering
Genetic Vectors
Humans
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Organ Specificity
Vaccines, Synthetic
Viral Vaccines
Virus Replication
Adenoviridae
Human adenovirus
Human adenovirus type 49
To reference this document use:
http://resolver.tudelft.nl/uuid:089369fa-f5d7-416e-bb99-f064277befc4
DOI
https://doi.org/10.1099/vir.0.82079-0
TNO identifier
239515
ISSN
0022-1317
Source
Journal of General Virology, 87 (87), 2891-2899
Document type
article