Abstract
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.
Highlights
Infectious diseases have had profound and long-lasting impacts on the human race throughout history
Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are highly pathogenic viral diseases, the global burden of EHF and MHF is minor in comparison to other infectious diseases [1]; as we observed with the 2014 West Africa outbreak, EHF has the potential to cause large, multi-nation outbreaks resulting in significant mortality and economic devastation
A subsequent Marburg outbreak occurred in Kenya in 1987, where the index case had visited a cave and contracted the virus; in this case the disease was caused by a new strain of Marburgvirus; Ravn virus (RAVV)
Summary
Infectious diseases have had profound and long-lasting impacts on the human race throughout history. Epidemic threats are deepened by the emergence of new and uncharacterized infectious diseases, coupled with the ability to impact human health and the economy at a global scale. Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are highly pathogenic viral diseases, the global burden of EHF and MHF is minor in comparison to other infectious diseases [1]; as we observed with the 2014 West Africa outbreak, EHF has the potential to cause large, multi-nation outbreaks resulting in significant mortality and economic devastation. We will discuss the history and pathogenesis of filoviruses, highlight the role of antibodies in protection against filovirus infections, and examine the potential of viral vector-mediated expression of monoclonal antibodies (mAbs) as an alternative prophylactic strategy to enable long term passive immunity against filovirus infections
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