Human AdV-20-42-42, a promising novel adenoviral vector for gene therapy and vaccine product development

Mónika Z. Ballmann, Svjetlana Raus, Ruben Engelhart, Győző L. Kaján, Abdelaziz Beqqali, Patrick Wf Hadoke, Chantal Van Der Zalm, Tibor Papp, Lijo John, Selina Khan, Satish Boedhoe, Katarina Danskog, Lars Frängsmyr, Jerome Custers, Wilfried A.m. Bakker, Hilde M. Van Der Schaar, Niklas Arnberg, Angelique A.c. Lemckert, Menzo Havenga, Andrew H. Baker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Pre-existing immune responses towards adenoviral vector 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 to vectorize 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 response. 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.
Original languageEnglish
JournalJournal of Virology
Early online date1 Sep 2021
DOIs
Publication statusE-pub ahead of print - 1 Sep 2021

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