PT  - JOURNAL ARTICLE
AU  - Yue Du
AU  - Kamran M Miah
AU  - Omar Habib
AU  - Helena Meyer-Berg
AU  - Catriona C Conway
AU  - Mariana A Viegas
AU  - Rebecca Dean
AU  - Dwiantari Satyapertiwi
AU  - Jincun Zhao
AU  - Yanqun Wang
AU  - Nigel J Temperton
AU  - Toby P E Gamlen
AU  - Deborah R Gill
AU  - Stephen C Hyde
TI  - Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection
AID  - 10.1136/thoraxjnl-2021-217650
DP  - 2022 Feb 13
TA  - Thorax
PG  - thoraxjnl-2021-217650
4099  - http://thorax.bmj.com/content/early/2022/02/13/thoraxjnl-2021-217650.short
4100  - http://thorax.bmj.com/content/early/2022/02/13/thoraxjnl-2021-217650.full
AB  - 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.All data relevant to the study are included in the article or uploaded as supplementary information.