Print Email Facebook Twitter Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49 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 Researchadenovirus vectorcell receptorGag proteinluciferasemembrane cofactor proteinneutralizing antibodyvirus vaccineadultagedanimal cellanimal experimentantibody titerarticleCD8+ T lymphocytecell linecontrolled studycross reactiongene constructheterozygotehumanHuman adenovirus 5human cellimmunogenicitymarker genemousenonhumannucleotide sequenceplasmidpriority journalseroprevalenceserotypeSimian immunodeficiency virusvirus replicationAdenoviruses, HumanAnimalsAntibodies, ViralAntigens, CD46Cell LineGenetic EngineeringGenetic VectorsHumansMiceMice, Inbred C57BLMolecular Sequence DataOrgan SpecificityVaccines, SyntheticViral VaccinesVirus ReplicationAdenoviridaeHuman adenovirusHuman 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 Files To receive the publication files, please send an e-mail request to TNO Library.