Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice
Vaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative appro...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Frontiers Media
2022
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| _version_ | 1797106657376862208 |
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| author | Du, Y Zhang, S Zhang, Z Miah, KM Wei, P Zhang, L Zhu, Y Li, Z Ye, F Gill, DR Hyde, SC Wang, Y Zhao, J |
| author_facet | Du, Y Zhang, S Zhang, Z Miah, KM Wei, P Zhang, L Zhu, Y Li, Z Ye, F Gill, DR Hyde, SC Wang, Y Zhao, J |
| author_sort | Du, Y |
| collection | OXFORD |
| description | Vaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative approach that does not wholly depend on individuals having intact immune systems and responses. Here, we identified an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody, NC0321, which can efficiently neutralize a range of SARS-CoV-2 variants, including alpha, beta, delta, and eta. Both prophylactic and therapeutic NC0321 treatments effectively protected mice from SARS-CoV-2 infection. Notably, we adopted viral vector-mediated delivery of NC0321 IgG1 as an attractive approach to prevent SARS-CoV-2 infection. The NC0321 IgG1 expression in the proximal airway, expressed by a single direct in-vivo intranasal (I.N.) administration of a self-inactivating and recombinant lentiviral vector (rSIV.F/HN-NC0321), can protect young, elderly, and immunocompromised mice against mouse-adapted SARS-CoV-2 surrogate challenge. Long-term monitoring indicated that rSIV.F/HN-NC0321 mediated robust IgG expression throughout the airway of young and SCID mice, importantly, no statistical difference in the NC0321 expression between young and SCID mice was observed. A single I.N. dose of rSIV.F/HN-NC0321 30 or 180 days prior to SARS-CoV-2 challenge significantly reduced lung SARS-CoV-2 titers in an Ad5-hACE2-transduced mouse model, reconfirming that this vectored immunoprophylaxis strategy could be useful, especially for those individuals who cannot gain effective immunity from existing vaccines, and could potentially prevent clinical sequelae. |
| first_indexed | 2024-03-07T07:04:09Z |
| format | Journal article |
| id | oxford-uuid:0a008c18-cfd7-4f5d-8819-5251817e3c88 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:04:09Z |
| publishDate | 2022 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:0a008c18-cfd7-4f5d-8819-5251817e3c882022-05-03T12:08:27ZIntranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0a008c18-cfd7-4f5d-8819-5251817e3c88EnglishSymplectic ElementsFrontiers Media2022Du, YZhang, SZhang, ZMiah, KMWei, PZhang, LZhu, YLi, ZYe, FGill, DRHyde, SCWang, YZhao, JVaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative approach that does not wholly depend on individuals having intact immune systems and responses. Here, we identified an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody, NC0321, which can efficiently neutralize a range of SARS-CoV-2 variants, including alpha, beta, delta, and eta. Both prophylactic and therapeutic NC0321 treatments effectively protected mice from SARS-CoV-2 infection. Notably, we adopted viral vector-mediated delivery of NC0321 IgG1 as an attractive approach to prevent SARS-CoV-2 infection. The NC0321 IgG1 expression in the proximal airway, expressed by a single direct in-vivo intranasal (I.N.) administration of a self-inactivating and recombinant lentiviral vector (rSIV.F/HN-NC0321), can protect young, elderly, and immunocompromised mice against mouse-adapted SARS-CoV-2 surrogate challenge. Long-term monitoring indicated that rSIV.F/HN-NC0321 mediated robust IgG expression throughout the airway of young and SCID mice, importantly, no statistical difference in the NC0321 expression between young and SCID mice was observed. A single I.N. dose of rSIV.F/HN-NC0321 30 or 180 days prior to SARS-CoV-2 challenge significantly reduced lung SARS-CoV-2 titers in an Ad5-hACE2-transduced mouse model, reconfirming that this vectored immunoprophylaxis strategy could be useful, especially for those individuals who cannot gain effective immunity from existing vaccines, and could potentially prevent clinical sequelae. |
| spellingShingle | Du, Y Zhang, S Zhang, Z Miah, KM Wei, P Zhang, L Zhu, Y Li, Z Ye, F Gill, DR Hyde, SC Wang, Y Zhao, J Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice |
| title | Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice |
| title_full | Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice |
| title_fullStr | Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice |
| title_full_unstemmed | Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice |
| title_short | Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice |
| title_sort | intranasal lentiviral vector mediated antibody delivery confers reduction of sars cov 2 infection in elderly and immunocompromised mice |
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