Preprint Article Version 2 This version is not peer-reviewed

In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

Version 1 : Received: 5 July 2021 / Approved: 6 July 2021 / Online: 6 July 2021 (13:33:31 CEST)
Version 2 : Received: 22 July 2021 / Approved: 22 July 2021 / Online: 22 July 2021 (09:45:08 CEST)

How to cite: Bates, E.A.; Counsell, J.R.; Alizert, S.; Baker, A.T.; Suff, N.; Boyle, A.; Bradshaw, A.C.; Waddington, S.N.; Nicklin, S.A.; Baker, A.H.; Parker, A.L. In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications. Preprints 2021, 2021070153 (doi: 10.20944/preprints202107.0153.v2). Bates, E.A.; Counsell, J.R.; Alizert, S.; Baker, A.T.; Suff, N.; Boyle, A.; Bradshaw, A.C.; Waddington, S.N.; Nicklin, S.A.; Baker, A.H.; Parker, A.L. In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications. Preprints 2021, 2021070153 (doi: 10.20944/preprints202107.0153.v2).

Abstract

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

Subject Areas

Adenovirus; viral vector; gene therapy; vaccines

Comments (1)

Comment 1
Received: 22 July 2021
Commenter: Alan Parker
Commenter's Conflict of Interests: Author
Comment: In response to reviewers, we quantified all IVIS images, and added a supple mental file including bar charts of the individual cyotokine profiles depicted in the table in figure 2.  We added a Coomassie gel to show the correct size and trimerisation of the fiber knob proteins used in figure 5. We added some comments throughout to clarify comments made by the reviewer, including a request to introduce FX and it's influence in the discussion (lines 55-66).
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