AAV Vectored Immunoprophylaxis for Filovirus Infections
Filoviruses are among the deadliest infectious agents known to man, causing severe hemorrhagic fever, with up to 90% fatality rates. The 2014 Ebola outbreak in West Africa resulted in over 28,000 infections, demonstrating the large-scale human health and economic impact generated by filoviruses. <...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Tropical Medicine and Infectious Disease |
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| Online Access: | https://www.mdpi.com/2414-6366/5/4/169 |
| _version_ | 1797548391046053888 |
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| author | Amira D. Rghei Laura P. van Lieshout Lisa A. Santry Matthew M. Guilleman Sylvia P. Thomas Leonardo Susta Khalil Karimi Byram W. Bridle Sarah K. Wootton |
| author_facet | Amira D. Rghei Laura P. van Lieshout Lisa A. Santry Matthew M. Guilleman Sylvia P. Thomas Leonardo Susta Khalil Karimi Byram W. Bridle Sarah K. Wootton |
| author_sort | Amira D. Rghei |
| collection | DOAJ |
| description | Filoviruses are among the deadliest infectious agents known to man, causing severe hemorrhagic fever, with up to 90% fatality rates. The 2014 Ebola outbreak in West Africa resulted in over 28,000 infections, demonstrating the large-scale human health and economic impact generated by filoviruses. <i>Zaire ebolavirus</i> is responsible for the greatest number of deaths to date and consequently there is now an approved vaccine, Ervebo, while other filovirus species have similar epidemic potential and remain without effective vaccines. Recent clinical success of REGN-EB3 and mAb-114 monoclonal antibody (mAb)-based therapies supports further investigation of this treatment approach for other filoviruses. While efficacious, protection from passive mAb therapies is short-lived, requiring repeat dosing to maintain therapeutic concentrations. An alternative strategy is vectored immunoprophylaxis (VIP), which utilizes an adeno-associated virus (AAV) vector to generate sustained expression of selected mAbs directly in vivo. This approach takes advantage of validated mAb development and enables vectorization of the top candidates to provide long-term immunity. In this review, we summarize the history of filovirus outbreaks, mAb-based therapeutics, and highlight promising AAV vectorized approaches to providing immunity against filoviruses where vaccines are not yet available. |
| first_indexed | 2024-03-10T14:58:42Z |
| format | Article |
| id | doaj.art-46be403b99ab488583d634e852cda2bd |
| institution | Directory Open Access Journal |
| issn | 2414-6366 |
| language | English |
| last_indexed | 2024-03-10T14:58:42Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Tropical Medicine and Infectious Disease |
| spelling | doaj.art-46be403b99ab488583d634e852cda2bd2023-11-20T20:19:48ZengMDPI AGTropical Medicine and Infectious Disease2414-63662020-11-015416910.3390/tropicalmed5040169AAV Vectored Immunoprophylaxis for Filovirus InfectionsAmira D. Rghei0Laura P. van Lieshout1Lisa A. Santry2Matthew M. Guilleman3Sylvia P. Thomas4Leonardo Susta5Khalil Karimi6Byram W. Bridle7Sarah K. Wootton8Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaFiloviruses are among the deadliest infectious agents known to man, causing severe hemorrhagic fever, with up to 90% fatality rates. The 2014 Ebola outbreak in West Africa resulted in over 28,000 infections, demonstrating the large-scale human health and economic impact generated by filoviruses. <i>Zaire ebolavirus</i> is responsible for the greatest number of deaths to date and consequently there is now an approved vaccine, Ervebo, while other filovirus species have similar epidemic potential and remain without effective vaccines. Recent clinical success of REGN-EB3 and mAb-114 monoclonal antibody (mAb)-based therapies supports further investigation of this treatment approach for other filoviruses. While efficacious, protection from passive mAb therapies is short-lived, requiring repeat dosing to maintain therapeutic concentrations. An alternative strategy is vectored immunoprophylaxis (VIP), which utilizes an adeno-associated virus (AAV) vector to generate sustained expression of selected mAbs directly in vivo. This approach takes advantage of validated mAb development and enables vectorization of the top candidates to provide long-term immunity. In this review, we summarize the history of filovirus outbreaks, mAb-based therapeutics, and highlight promising AAV vectorized approaches to providing immunity against filoviruses where vaccines are not yet available.https://www.mdpi.com/2414-6366/5/4/169monoclonal antibodiesadeno-associated virus vectorvectored-immunoprophylaxis (VIP)vector biologyfilovirusesviral hemorrhagic fever |
| spellingShingle | Amira D. Rghei Laura P. van Lieshout Lisa A. Santry Matthew M. Guilleman Sylvia P. Thomas Leonardo Susta Khalil Karimi Byram W. Bridle Sarah K. Wootton AAV Vectored Immunoprophylaxis for Filovirus Infections Tropical Medicine and Infectious Disease monoclonal antibodies adeno-associated virus vector vectored-immunoprophylaxis (VIP) vector biology filoviruses viral hemorrhagic fever |
| title | AAV Vectored Immunoprophylaxis for Filovirus Infections |
| title_full | AAV Vectored Immunoprophylaxis for Filovirus Infections |
| title_fullStr | AAV Vectored Immunoprophylaxis for Filovirus Infections |
| title_full_unstemmed | AAV Vectored Immunoprophylaxis for Filovirus Infections |
| title_short | AAV Vectored Immunoprophylaxis for Filovirus Infections |
| title_sort | aav vectored immunoprophylaxis for filovirus infections |
| topic | monoclonal antibodies adeno-associated virus vector vectored-immunoprophylaxis (VIP) vector biology filoviruses viral hemorrhagic fever |
| url | https://www.mdpi.com/2414-6366/5/4/169 |
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