An Immunoprotectant for Marburg Virus

DESCRIPTION provided by applicant Mortality rates associated with Marburg virus MARV outbreaks range from to over MARV is included by the Centers for Disease Control and Prevention as among the Category A agents or andquot high priority agents that pose a risk to national security andquot MARV not only causes acute and terrifying disease but it is relatively stable in wet or dry aerosols it is highly infectious whether infection occurs parenterally or by aerosol LD is approximately plaque forming unit it is subject to nosocomial and iatrogenic spread to and by health care personnel and as an endemic African virus it could be acquired from recurrent natural outbreaks by a resourceful individual or group There are currently no drugs available for preventing or treating infections with MARV There is a clear unmet need for a MARV immunoprotectant to address biowarfare threats as well as public health concerns raised by naturally occurring outbreaks Passive immunization with antibodies has been shown to be effective against a wide variety of viruses Because of their excellent safety profile and efficacy mAbs are a rapidly growing class of therapeutic drug We have shown that a cocktail of mAbs can provide post exposure and therapeutic protection against lethal challenge with another filovirus Ebola in the non human primate NHP model i e the model most representative of humans As a result of successful completion of our Phase SBIR efforts we have identified six potent anti MARV mAbs that protect mice from lethal challenge Further in this proposal we are combining forces with Integrated Biotherapeutics Dr Kelly Warfield Gaithersburg MD and the Public Health Agency of Canada PHAC Dr Gary Kobinger whose teams have identified additional protective mAbs via separate funding Together with Dr Tom Geisbert UTMB Galveston TX we will determine which of these combinations of mAbs is the most appropriate for continued development The Long Range Objective of this project is to develop a safe and effective immunoprotectant for Marburg virus In Specific Aim the existing protective mAbs will be produced using a well characterized transient Nicotiana production system Experiments in rodents will be used to select a lead mAb cocktail for advancement to non human primate NHP testing In Specific Aim the cocktail will be evaluated in NHPs against lethal MARV challenge In Specific Aim IND enabling testing will be completed and an IND submitted PUBLIC HEALTH RELEVANCE The efforts in this proposal will help in the development of a drug product for preventing and treating infection with Marburg virus a highly lethal virus that causes sporadic outbreaks and is a biowarfare threat