Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection
<p><strong>Background</strong> 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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022
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| _version_ | 1797108325030035456 |
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| author | Yue, D Miah, KM Habib, O Meyer-Berg, H Conway, CC Viegas, MA Dean, R Satyapertiwi, D Zhao, J Wang, Y Temperton, NJ Gamlen, TPE Gill, DR Hyde, SC |
| author_facet | Yue, D Miah, KM Habib, O Meyer-Berg, H Conway, CC Viegas, MA Dean, R Satyapertiwi, D Zhao, J Wang, Y Temperton, NJ Gamlen, TPE Gill, DR Hyde, SC |
| author_sort | Yue, D |
| collection | OXFORD |
| description | <p><strong>Background</strong> 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.</p>
<p><strong>Aims</strong> 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.</p>
<p><strong>Methods</strong> 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.</p>
<p><strong>Conclusions</strong> 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.</p> |
| first_indexed | 2024-03-07T07:27:35Z |
| format | Journal article |
| id | oxford-uuid:8f0c4f1c-525a-4f47-9cc2-33f78e64f021 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:27:35Z |
| publishDate | 2022 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:8f0c4f1c-525a-4f47-9cc2-33f78e64f0212022-11-28T10:34:47ZLung directed antibody gene transfer confers protection against SARS-CoV-2 infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8f0c4f1c-525a-4f47-9cc2-33f78e64f021EnglishSymplectic ElementsBMJ Publishing Group2022Yue, DMiah, KMHabib, OMeyer-Berg, HConway, CCViegas, MADean, RSatyapertiwi, DZhao, JWang, YTemperton, NJGamlen, TPEGill, DRHyde, SC<p><strong>Background</strong> 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.</p> <p><strong>Aims</strong> 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.</p> <p><strong>Methods</strong> 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.</p> <p><strong>Conclusions</strong> 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.</p> |
| spellingShingle | Yue, D Miah, KM Habib, O Meyer-Berg, H Conway, CC Viegas, MA Dean, R Satyapertiwi, D Zhao, J Wang, Y Temperton, NJ Gamlen, TPE Gill, DR Hyde, SC Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection |
| title | Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection |
| title_full | Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection |
| title_fullStr | Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection |
| title_full_unstemmed | Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection |
| title_short | Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection |
| title_sort | lung directed antibody gene transfer confers protection against sars cov 2 infection |
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