Tuesday, October 21, 2014

Excellent review of experimental vaccine and drug approaches to Ebola/ 2nd Canadian drug review

I read the full text but can't post it due to copyright.  The first review is from U Texas. 

 2013 Dec;27(6):565-83. doi: 10.1007/s40259-013-0046-1.
Emerging Targets and Novel Approaches to Ebola Virus Prophylaxis and Treatment


Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant adenovirus-based vectors have been identified as potent vaccine candidates, with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the US Food and Drug Administration (FDA) and phase I clinical trials have been initiated for two small-molecule therapeutics: anti-sense phosphorodiamidate morpholino oligomers (PMOs: AVI-6002, AVI-6003) and lipid nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy, which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebolahemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms are also discussed.

From Canada's Special Pathogens Lab:

 2014 Aug;22(8):456-63. doi: 10.1016/j.tim.2014.04.002. Epub 2014 Apr 30.
Post-Exposure Therapy of Filovirus Infections


Filovirus infections cause fatal hemorrhagic fever characterized by the initial onset of general symptoms before rapid progression to severe disease; the most virulent species can cause death to susceptible hosts within 10 days after the appearance of symptoms. Before the advent of monoclonal antibody (mAb) therapy, infection of nonhuman primates (NHPs) with the most virulent filovirus species was fatal if interventions were not administered within minutes. A novel nucleoside analogue, BCX4430, has since been shown to also demonstrate protective efficacy with a delayed treatment start. This review summarizes and evaluates the potential of current experimental candidates for treating filovirus disease with regard to their feasibility and use in the clinic, and assesses the most promising strategies towards the future development of a pan-filovirus medical countermeasure.

This review from USAMRIID.  You can get the free full text here.

 2012 Sep;4(9):1619-50. doi: 10.3390/v4091619. Epub 2012 Sep 21.
Potential vaccines and post-exposure treatments for filovirus infections

  • 1United States Army Medical Research Institute of Infectious Diseases, Division of Virology, Frederick, MD 21702, USA. brian.m.friedrich.ctr@us.army.mil


Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.

No comments: