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Review

AAV Vectored Immunoprophylaxis for Filovirus Infections

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
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Author to whom correspondence should be addressed.
Trop. Med. Infect. Dis. 2020, 5(4), 169; https://doi.org/10.3390/tropicalmed5040169
Received: 1 October 2020 / Revised: 5 November 2020 / Accepted: 6 November 2020 / Published: 9 November 2020
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. Zaire ebolavirus 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. View Full-Text
Keywords: monoclonal antibodies; adeno-associated virus vector; vectored-immunoprophylaxis (VIP); vector biology; filoviruses; viral hemorrhagic fever; zoonotic diseases monoclonal antibodies; adeno-associated virus vector; vectored-immunoprophylaxis (VIP); vector biology; filoviruses; viral hemorrhagic fever; zoonotic diseases
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MDPI and ACS Style

Rghei, A.D.; van Lieshout, L.P.; Santry, L.A.; Guilleman, M.M.; Thomas, S.P.; Susta, L.; Karimi, K.; Bridle, B.W.; Wootton, S.K. AAV Vectored Immunoprophylaxis for Filovirus Infections. Trop. Med. Infect. Dis. 2020, 5, 169. https://doi.org/10.3390/tropicalmed5040169

AMA Style

Rghei AD, van Lieshout LP, Santry LA, Guilleman MM, Thomas SP, Susta L, Karimi K, Bridle BW, Wootton SK. AAV Vectored Immunoprophylaxis for Filovirus Infections. Tropical Medicine and Infectious Disease. 2020; 5(4):169. https://doi.org/10.3390/tropicalmed5040169

Chicago/Turabian Style

Rghei, Amira D., Laura P. van Lieshout, Lisa A. Santry, Matthew M. Guilleman, Sylvia P. Thomas, Leonardo Susta, Khalil Karimi, Byram W. Bridle, and Sarah K. Wootton. 2020. "AAV Vectored Immunoprophylaxis for Filovirus Infections" Tropical Medicine and Infectious Disease 5, no. 4: 169. https://doi.org/10.3390/tropicalmed5040169

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