Dr. Eva Harris is co-leader of major pandemic preparedness project
Research Consortium Awarded Five-Year Grant for $14 M per Year
- 5 min. read ▪ Published
An Albert Einstein College of Medicine-led research consortium has received a five-year, $14 million per year grant from the National Institute of Allergy and Infectious Diseases (NIAID) to participate in a broad national effort to develop “plug-and-play” vaccines and antibody-based therapies against a wide range of emerging viruses. The grant is part of NIAID’s new Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) Network, which was announced earlier today.
“COVID-19 taught us a lot about pandemic preparedness, and we want to make sure we build on what worked well,” said Kartik Chandran, PhD, the principal investigator on the grant and professor of microbiology & immunology, the Gertrude and David Feinson Chair in Medicine, and the Harold and Muriel Block Faculty Scholar in Virology at Einstein. “One of the key lessons from the COVID pandemic is that having existing research on a viral family allows scientists to develop vaccines and therapeutics for a particular virus much more quickly. In our project, we plan to create a base of critical knowledge about groups of similar viruses and then—should a related ‘virus X’ pose a health threat—develop specific countermeasures as quickly as possible to save as many lives as possible.”
The Einstein-led consortium, called PROVIDENT (Prepositioning Optimized Strategies for Vaccines and Immunotherapeutics Against Diverse Emerging Infectious Threats), will link 13 teams in academia, government, and industry that will conduct four projects designed to:
- Discover and analyze virus-host interactions and the molecular mechanisms involved in viral disease;
- Design proteins to elicit antiviral immune responses and then evaluate and optimize those responses;
- Create “road maps” for quickly developing RNA vaccines against microbes with pandemic potential; and
- Map the antibody responses observed in people infected with viruses and use this knowledge to design vaccines and therapeutics.
Dr. Eva Harris, professor and chair of infectious diseases and vaccinology at UC Berkeley School of Public Health, is co-leading PROVIDENT’s Project 1, which focuses on the discovery and dissection of virus-host interactions and pathogenic mechanisms. Her group’s contribution enhanced the innovation of the program, as it extends a novel discovery out of Harris lab at UC Berkeley.
“We discovered that there are secreted viral proteins, which we dubbed viral toxins, that cause vascular leak and aid viral dissemination in hosts infected by mosquito-borne viruses like dengue and Zika,” said Harris. The protein itself can cause injury, with or without the virus.
“We had an insight that the secreted GP38 protein from the Crimean Congo hemorrhagic fever bunyavirus could also be acting as a viral toxin, which we showed was indeed the case, working in collaboration with Dr. Chandran at Einstein and others from the PROVIDENT team, led by PhD student Felix Pahmeier in my lab. This is a novel mechanism of pathogenesis [the process by which an infection leads to disease], and it opens a whole new avenue in vaccines, which are being explored in the current grant.”
PROVIDENT builds on NIAID’s 2021 Pandemic Preparedness Plan, a sweeping federal program designed to address the uncertainties inherent in safeguarding global health from communicable diseases. The two-part plan focuses on “priority pathogens” and “prototype pathogens”—basically, the knowns and unknowns of the viral world. Priority pathogens include viruses that are known to cause significant human illness or death, such as dengue virus and Ebola virus.
Prototype pathogens—the focus of PROVIDENT—are representative viruses in families that have the potential to cause significant human disease. “We plan to select and study one or two prototype viruses from each family and then develop countermeasures that will work against as many viruses within that family as possible,” said Dr. Chandran. “That strategy of quickly responding to an emerging virus with an approach and tools that have already been developed is what we mean by ‘plug and play’.” A part of PROVIDENT’s strategy will be to carry out “sprints” in which countermeasures that are developed for the prototype pathogens will be tested against other viruses in the same family to see how well they work and to improve them.
PROVIDENT will concentrate on three virus families: nairoviruses, transmitted by ticks (e.g., Crimean-Congo hemorrhagic fever virus), hantaviruses, borne by rodents and other small mammals (e.g., Sin Nombre virus and other agents causing hantavirus pulmonary syndrome), and paramyxoviruses, borne by bats and other mammals, including domesticated animals (e.g., Nipah virus).
“This approach allowed researchers to move quickly during the COVID-19 pandemic,” said Dr. Chandran. “What we had learned from previous outbreaks caused by coronaviruses, including SARS [severe acute respiratory syndrome] in 2002 and MERS [Middle Eastern respiratory syndrome] a decade later, helped us create diagnostics, vaccines, and therapeutics against SARS-CoV-2, the virus that causes COVID-19.”
“Recent outbreaks of Mpox, Nipah virus, and Eastern equine encephalitis, among other viral infections, underscore the need for an even broader preparedness program,” said Eva Mittler, PhD, research assistant professor at Einstein and leader of one of the PROVIDENT components. “We don’t know what virus will cause the next pandemic.”
“The overarching goal of PROVIDENT and the other centers in the ReVAMPP Network is to coordinate their efforts to increase our odds of mounting a timely and effective response,” added Dr. Chandran.