Pandemic preparedness research and biocontainment infrastructure at The Rockefeller University

Project Summary/Abstract Rockefeller University is a unique institution: with only 70 Heads of Laboratories, the faculty have received 3 Nobel prizes in Medicine in the last 10 years and 5 (plus 1 in chemistry) in the last 21 years, along with appointment of 18 faculty as HHMI investigators and 29 to membership in the National Academy of Sciences. Rockefeller faculty have played an outsized role in contributions to foundational discoveries in virology and infectious disease, both historically and presently. Recognizing the importance of the current pandemic, over the past two years, a dozen research groups at Rockefeller have joined the research efforts focused on pandemic threat viruses, with numerous grants supporting the work and over 50 peer-reviewed publications to date. Rockefeller labs have made seminal contributions identifying the spectrum of neutralizing antibodies to the SARS-CoV-2 spike protein, the impact of variants on neutralization, and characterizing the atomic- resolution binding of antibodies to spike protein. Collectively, Rockefeller laboratories are working on Alphaviruses (e.g., Sindbis, chikungunya viruses), Flaviviruses (e.g., yellow fever, Zika, West Nile, Powassan viruses), Hepaciviruses (hepatitis C virus, Norway rat hepacivirus), Hepadnaviruses (hepatitis B virus), Orthomyxoviruses (influenza), Coronaviruses (SARS-CoV-2 and other human coronaviruses) and retroviruses including HIV-1. Many of the viruses under study, including chikungunya, yellow fever, West Nile, Powassan, and SARS-CoV-2, are classified as Risk Group 3 (RG3) pathogens, requiring BSL3 containment facilities and practices. Moreover, some research at Rockefeller includes the generation of replicons and chimeric (VSV- based) viruses whose stability and safety should be established under BSL3 conditions prior to use at lower biosafety containment levels. This project seeks to enhance and expand space and support for both in vivo and in vitro research. Specific aim 1 is to increase the Rockefeller University's BSL3 capacities to meet the scientific needs by establishing a new BSL3 facility in an existing laboratory building. Specific aim 2 is to equip and enhance the new facility and the BSL3/ABSL3 facilities that already exist at the University. To achieve these aims, an extremely experienced team of personnel at Rockefeller propose to: establish a new multiple- investigator BSL3 facility; add equipment to the existing single-PI BSL3 facility; replace an existing autoclave and add an incremental autoclave in the ABSL3; and modernize the supporting infrastructure in the ABSL3.