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Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection

Du, Yue, Miah, Kamram M., Habib, Omar, Meyer-Berg, Helena, Conway, Catriona C., Viegas, Mariana A., Dean, Rebecca, Satyapertiwi, Dwiantari, Zhao, Jincun, Wang, Yanqun, and others. (2022) Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection. Thorax, . ISSN 0040-6376. (KAR id:91980)

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Abstract

The novel coronavirus disease (COVID-19) pandemic continues to be a worldwide threat and effective antiviral drugs and vaccines are being developed in a joint global effort. However, some elderly and immune-compromised populations are unable to raise an effective immune response against traditional vaccines. We hypothesised that passive immunity engineered by the in vivo expression of anti SARS-CoV-2 monoclonal antibodies (mAbs), an approach termed vectored immunoprophylaxis (VIP), could offer sustained protection against COVID-19 in all populations irrespective of their immune status or age. We developed three key reagents to evaluate VIP for SARS-CoV-2: (i) we engineered standard laboratory mice to express human ACE2 via rAAV9 in vivo gene transfer, to allow in vivo assessment of SARS-CoV-2 infection, (ii) to simplify in vivo challenge studies, we generated SARS-CoV-2 Spike protein pseudotyped lentiviral vectors as a simple mimic of authentic SARS-CoV-2 that could be used under standard laboratory containment conditions; and (iii) we developed in vivo gene transfer vectors to express anti-SARS-CoV-2 mAbs. A single intranasal dose of rAAV9 or rSIV.F/HN vectors expressing anti-SARS-CoV 2 mAbs significantly reduced SARS-CoV-2 mimic infection in the lower respiratory tract of hACE2-expressing mice. If translated, the VIP approach could potentially offer a highly effective, long-term protection against COVID-19 for highly vulnerable populations; especially immune-deficient/senescent individuals, who fail to respond to conventional SARS-CoV 2 vaccines. The in vivo expression of multiple anti-SARS71 CoV-2 mAbs could enhance protection and prevent rapid mutational escape.

Item Type: Article
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 03 Dec 2021 12:30 UTC
Last Modified: 15 Feb 2022 21:37 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91980 (The current URI for this page, for reference purposes)
Temperton, Nigel J.: https://orcid.org/0000-0002-7978-3815
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