From Surveillance to Bedside: Tools for the Next Outbreak

By Michael Krug

The recent emergence of the novel Coronavirus (nCoV) hdemonstrates an essential demand for tools to rapidly respond to infectious diseases. These tools range from improved disease surveillance to therapeutics that mitigate infection spread. As new emerging diseases continue challenging global health response, it is imperative that these technologies continue to be developed, tested, and licensed for global use. This session, moderated by Dr. Vineet Menachery of the University of Texas Medical Branch and Dr. Kari Debbink of Bowie State University, touched on cutting edge research for the response to the next emerging infectious disease.

First to present was Dr. Amy Hartman from the University of Pittsburgh. Dr. Hartman’s presentation was titled In Utero: Transmission of Rift Valley Fever Virus: Ramifications for Future Outbreaks. The takeaway of Dr. Hartman’s presentation revolved around the use of animal models to better understand vaccine and therapeutic effectiveness. One of the projects investigating viable models involved using Rift Valley Fever Virus (RVFV), a select agent and priority disease declared by WHO, to test for vertical transmission of the disease in pregnant women. Limited human outbreak data suggest that vertical transmission of RVFV to a developing human fetus can lead to detrimental outcomes. In order to complete this study, a tested and validated animal model was needed, a difficult task to achieve given the human fetal tissue bans. Using immunocompetent Sprague-Dawley rats infected with a pathogenic strain of RVFV, Dr. Hartman’s lab demonstrated direct vertical transmission, which included fetal death. Additionally, the lab used donated placental explants to show RVFV replication in human cells that are typically resistant to viral infection. With the in vivo model and human placental cell evidence, Dr. Hartman’s lab demonstrated RVFV replication in the human placenta cells, as well as vertical transmission of RVFV in a novel animal model.

The next presenter, Dr. Kartik Chandran from Albert Einstein College of Medicine, described the urgent need for broad spectrum  antibody therapeutics protective against multiple filoviruses. In his presentation, Human Antibody Therapeutics against Emerging RNA Viruses, Dr. Chandran elucidates the high clade variability filoviruses, like Ebola and Marburg viruses. This high variability makes it difficult to develop broad spectrum antivirals. One of the primary targets of these viruses is the rapidly-mutating viral glycoprotein (GP). Dr. Chandran’s lab identified a broadly neutralizing human monoclonal antibodies (mAb) cocktail, known as MBP134, effective against several Ebola virus species. The cocktail includes two broadly neutralizing human mAbs, the first is from an Ebola virus survivor and the second is from the same survivor but with specificity-matured for Sudan virus GP binding affinity. A single dose cleared virus from the blood and reversed inflammation markers and liver damage. This is a novel therapeutic, since all other mAbs that have entered clinical development are specific for a single member of the Ebola virus genus. In addition to developing a novel Ebola therapeutic, Dr. Chandran’s selection process for effective mAbs was used to advance therapeutics for Crimean-Congo hemorrhagic fever virus and hantaviruses, like hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. Building out antibody selective processes can help streamline the timeline for effective treatments against emerging infectious diseases.

The final presenter was Dr. Timothy Sheahan from the University of North Carolina-Chapel Hill. His timely presentation was on Broad-Spectrum Therapeutics to Prevent Coronavirus Epidemic Disease. Recognizing the importance of the topic, Dr. Sheahan did an excellent job of providing an overview of previous highly publicized coronavirus outbreaks, like SARS and MERS. He drew particular attention to the fact that global travel allows for fast-moving pandemics, especially involving coronaviruses. With the mortality rates of SARS at approximately 10%, and MERS at about 35% of those infected with the virus, Dr. Sheahan made it evident that streamlining therapeutic development was imperative. Due to the zoonotic nature of coronaviruses, they can infect a variety of animal reservoirs and eventually spillover into humans. The emergence of nCoV has further supported the need for broad spectrum therapeutics that can protect against known and unknown viruses. Dr. Sheahan’s lab has begun to move away from the idea of “one drug, one bug approach” and instead aims to uncover “one drug for many bugs approach.” This approach was exemplified through his work with Remdesivir, an antiviral developed as a treatment for Ebola and Marburg virus diseases. Through the pre-clinical human and mouse models, the lab confirmed effective viral clearance of both SARS and MERS viruses, with Remdesivir. Both antivirals were tested as a prophylaxis (one day prior to infection) and therapeutic (one day post infection). Altogether, these data suggest that antiviral treatments could have broad spectrum activity in emerging infectious diseases, particularly coronaviruses.

I found this session to be tremendously practical in describing the significance of cutting edge basic science efforts. In particular, research aimed at combatting infectious diseases. Foundational research can often be overlooked, but these three projects exemplify the importance of infectious disease research for impactful real-world applications.