Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection. Issue 12 (14th February 2022)

• Record Type: Journal Article
• Authors: Du, Yue; Miah, Kamran M; Habib, Omar; Meyer-Berg, Helena; Conway, Catriona C; Viegas, Mariana A; Dean, Rebecca; Satyapertiwi, Dwiantari; Zhao, Jincun; Wang, Yanqun; Temperton, Nigel J; Gamlen, Toby P E; Gill, Deborah R; Hyde, Stephen C
• Is Part Of: Thorax. Volume 77:Issue 12(2022)
• Page Start: 1229
• Page End: 1236
• Publication Date: 2022-02-14
• Subjects: COVID-19 -- respiratory infection -- viral infection; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2021-217650
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Background: The 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. Aims: 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. Methods: 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. Conclusions: 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-SARS-CoV-2 mAbs could enhance protection and prevent rapid mutational escape.