WU-22-0241

SCOPE OF WORK SUBCONTRACTOR SUBCONTRACT PI: JAMES CROWE INSTITUTION: VANDERBILT UNIVERSITY MEDICAL CENTER CONTRACT INFORMATION SOLICITATION: BAA-NIAID-DAIT- NIHAI201800001, B-CELL EPITOPE DISCOVERY AND MECHANISMS OF ANTIBODY PROTECTION DATES OF PERFORMANCE: 10/1/19-9/30/24 PROJECT PI: DAVID FREMONT, PHD, WASHINGTON UNIVERSITY IN ST. LOUIS WORK TO BE PERFORMED: ACQUIRE HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM THE VANDERBILT VACCINE CENTER BIOREPOSITORY FROM SUBJECTS WITH PRIOR INFECTION OR IMMUNIZATION FOR FLAVIVIRUSES OR ALPHAVIRUSES ACTIVATE HUMAN B CELLS IN CULTURE TO IDENTIFY VIRUS-SPECIFIC ANTIBODY SECRETING CELL LINES AND DETERMINE THE FREQUENCY OF SUCH B CELLS IN DONOR SAMPLES IMMORTALIZE VIRUS-SPECIFIC ANTIBODY SECRETING CELL LINES PRODUCE HUMAN MONOCLONAL ANTIBODIES TO THE TARGETS ABOVE, 25 MAB FUSION EXPERIMENTS PER TARGET PRODUCE PURIFIED IMMUNOGLOBULINS FOR EACH HUMAN MONOCLONAL ANTIBODY OBTAINED SHIP PURIFIED IMMUNOGLOBULINS TO THE PRIME CONTRACT SITE PARTICIPATE IN COLLABORATION CALLS ON A REGULAR BASIS VANDERBILT UNIVERSITY MEDICAL CENTER JAMES CROWE RESPONSIBILITIES: DR. CROWE IS AN IMMUNOLOGIST, INFECTIOUS DISEASES PHYSICIAN AND EXPERT IN VIRUS-SPECIFIC ANTIBODY RESPONSES IN ADULTS AND CHILDREN. HE HAS PIONEERED TECHNOLOGIES FOR SORTING AND ANALYZING VIRUS-SPECIFIC B CELLS AND GENERATING ANTIVIRAL HUMAN MONOCLONAL ANTIBODIES AND WILL APPLY THESE UNIQUE TECHNOLOGIES TOWARD THE ISOLATION OF ANTIVIRAL HUMAN MONOCLONAL ANTIBODIES FOR THE TARGETS PROPOSED IN THE WUSTL APPLICATION. FORTUNATELY, THE HUMAN SUBJECTS PROGRAM IN THE VANDERBILT VACCINE CENTER (VVC) HAS COLLECTED PBMCS UNDER APPROVED PROTOCOLS FOLLOWING WRITTEN INFORMED CONSENT, AND DEPOSITED DE-IDENTIFIED PBMC COLLECTIONS INTO THE VVC BIOREPOSITORY. THUS, WE HAVE THE HUMAN SAMPLES WE NEED TO MAKE HUMAN MONOCLONAL ANTIBODIES FOR YOUR PROPOSED PROJECTS, WITHOUT HAVING TO DO ADDITIONAL HUMAN SUBJECT STUDIES. WE WILL MAKE PANELS OF DIVERSE HUMAN MONOCLONAL ANTIBODIES FOR THESE THREE TARGETS AND PROVIDE YOUR TEAM PURIFIED MONOCLONAL IGG AND FAB FOR THE CLONES OF INTEREST. WE WILL PRIORITIZE POTENTLY NEUTRALIZING AND CROSS-REACTIVE ANTIBODIES ( PAN-FLAVI OR PAN-ALPHA ), BUT ALSO WE CAN PROVIDE NON-NEUTRALIZING CLONES, WHICH MAY CONTRIBUTE TO PROTECTION BY ALTERNATE MECHANISMS. DESCRIPTION OF SERVICES: DR. CROWE WILL ACQUIRE HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM THE VANDERBILT VACCINE CENTER BIOREPOSITORY FROM SUBJECTS WITH PRIOR INFECTION OR IMMUNIZATION FOR FLAVIVIRUSES OR ALPHAVIRUSES. HE WILL ACTIVATE HUMAN B CELLS IN CULTURE TO IDENTIFY AND IMMORTALIZE VIRUS-SPECIFIC ANTIBODY SECRETING CELL LINES. HE WILL SUPPLY LARGE PANELS OF PURIFIED HUMAN MONOCLONAL ANTIBODIES FOR B CELL MAPPING AND FUNCTIONAL EVALUATION. HE CAN PROVIDE THE ANTIBODIES AS IGG OR FABS, WHICH IS THE PREFERRED FORMAT FOR BIOPHYSICAL INVESTIGATIONS. HE WILL ALSO PROVIDE ANTIBODY SEQUENCES WHICH ARE ESSENTIAL WHEN UNDERTAKING STRUCTURAL BIOLOGY EXPERIMENTS. MAB GENERATION. LARGE PANELS OF HUMAN MABS AGAINST TARGET ANTIGENS WILL BE GENERATED. DR. JAMES CROWE (VU) WILL DEVELOP NEW HUMAN MABS TO DENGUE VIRUS SEROTYPE 4 (DENV-4), POWASSAN VIRUS (POWV), AND VENEZUELAN EQUINE ENCEPHALITIS (VEEV) USING DE-IDENTIFIED PBMCS FROM INFECTED AND/OR VACCINATED PATIENTS THAT ARE CURRENTLY AVAILABLE IN THE VANDERBILT VACCINE CENTER.

Vanderbilt University Medical Center

$358,040.00

Jan. 5, 2022

Nashville, Tennessee 37233-2007 United States

Washington University

SARS-CoV-2 B-Cell epitope mapping supplement

75N93019C00062

B CELL EPITOPE DISCOVERY AND MECHANISMS OF ANTIBODY PROTECTION

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Not Reported

AN12 - Health R&D Services; Health Care Services; Applied Research

Cost No Fee

Saint Louis, MO 63110 United States

None

Full And Open Competition