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Human AdV-20-42-42, a promising novel adenoviral vector for gene therapy and vaccine product development
Batavia Biosciences B.V., Leiden, Netherlands.
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Batavia Biosciences B.V., Leiden, Netherlands; Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.ORCID-id: 0000-0001-8213-8238
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2021 (Engelska)Ingår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 95, nr 22, artikel-id e00387-21Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Preexisting immune responses toward adenoviral vectors limit the use of a vector based on particular serotypes and its clinical applicability for gene therapy and/or vaccination. Therefore, there is a significant interest in vectorizing novel adenoviral types that have low seroprevalence in the human population. Here, we describe the discovery and vectorization of a chimeric human adenovirus, which we call HAdV-20-42-42. Full-genome sequencing revealed that this virus is closely related to human serotype 42, except for the penton base, which is derived from serotype 20. The HAdV-20-42-42 vector could be propagated stably to high titers on existing E1-complementing packaging cell lines. Receptor-binding studies revealed that the vector utilized both CAR and CD46 as receptors for cell entry. Furthermore, the HAdV-20-42-42 vector was potent in transducing human and murine cardiovascular cells and tissues, irrespective of the presence of blood coagulation factor X. In vivo characterizations demonstrate that when delivered intravenously (i.v.) in mice, HAdV-20-42-42 mainly targeted the lungs, liver, and spleen and triggered robust inflammatory immune responses. Finally, we demonstrate that potent T-cell responses against vector-delivered antigens could be induced upon intramuscular vaccination in mice. In summary, from the data obtained we conclude that HAdV-20-42-42 provides a valuable addition to the portfolio of adenoviral vectors available to develop efficacious products in the fields of gene therapy and vaccination.

Ort, förlag, år, upplaga, sidor
American Society for Microbiology , 2021. Vol. 95, nr 22, artikel-id e00387-21
Nyckelord [en]
Cell and tissue transduction, Expression vector, Low seroprevalence, Novel adenovirus serotype, Potent T-cell responses
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:umu:diva-189474DOI: 10.1128/JVI.00387-21ISI: 000718339200005PubMedID: 34469243Scopus ID: 2-s2.0-85118238152OAI: oai:DiVA.org:umu-189474DiVA, id: diva2:1611708
Forskningsfinansiär
EU, Horisont 2020, 825670EU, FP7, Sjunde ramprogrammet, 324325Tillgänglig från: 2021-11-16 Skapad: 2021-11-16 Senast uppdaterad: 2023-09-05Bibliografiskt granskad

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Kaján, Gyõzõ L.Lijo, JohnDanskog, KatarinaFrängsmyr, LarsArnberg, Niklas

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