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Principal Investigator: Margaret Juliana McElrath
Organization: FRED HUTCHINSON CANCER RESEARCH CENTER
Fiscal Year: 2020
Award: $29,952,323
Funding agency: National Institute of Allergy and Infectious Diseases
This proposal outlines the scientific agenda for the Leadership and Operations Center of the HIV Vaccine
Trials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4
continents dedicated to developing globally effective vaccines for HIV, tuberculosis and now SARS-CoV-2.
The HVTN has led HIV prevention science for over 20 years through robust phase 1 and 2 clinical
development trials and currently has 2 vector based vaccines (ALVAC and Ad26) and 1 broadly neutralizing
monoclonal antibody (mAb) VRC01 undergoing testing in 5 randomized controlled efficacy trials.
With the rapid onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in the
field on the contribution of immune functions involved in preventing infection, in modifying COVID-19 disease,
and in clearing viral infection. We believe the HVTN is well placed to study these gaps and rapidly deploy this
information in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study we
propose initiating an observational cohort study of approximately 400 persons in the United States (22 trials
sites) and Peru (5 sites) convalescing from SARS-CoV-2 infection. Participants will be recruited from a variety
of risk groups and clinical cohorts: hospitalized vs. non-hospitalized, symptomatic vs. asymptomatic, adults
between 18 and 55 years of age and those older than 55 years, and persons with high interest clinical or
virologic presentations (eg, persons who developed myocarditis/pericarditis, required intubation, had prolonged
viral shedding, or who develop a positive virologic test after initially clearing the infection). Specific aims of
this study include identifying serologic reactivities that differentiate SARS-CoV-2 infection from vaccination, to
develop and qualify a suite of immunologic assays and reference reagents that will permit detailed
interrogations of the immune response to infection, to measure SARS-CoV-2 adaptive response in key
populations and risk groups, and to characterize presentations of the infection among convalescent individuals.
This initial study will tell us much about the adaptive immune responses in persons who have been infected
and recovered from SARS-CoV-2 and will shed light on the role the immune system plays in successfully
clearance of infection. It will improve our understanding of the dynamics and duration of responses, as well as
the epitope specificity and other defining signatures, and will inform rational design and testing of preventive
and therapeutic vaccines and monoclonal antibodies. In addition, this protocol will lay the groundwork for
prospective studies of this infection, better defining key risk groups and knowledge gaps. Lastly, this study will
prepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline.
Laboratory, statistical and operational experience in this first trial will be invaluable preparation and priming of
network machinery as the HVTN prepare to roll-out several efficacy trials as part of the joint NIAID COVID
Prevention Network in coming months.
Terms: <2019 novel coronavirus><2019-nCoV><21+ years old><AIDS prevention><ALVAC><ALVAC Canarypox Vector><Abdominal Typhus><Acute><Adult><Adult Human><Age-Years><Antigenic Determinants><Assay><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><COVID><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID-19 vaccine><COVID19><COVID19 epidemic><COVID19 pandemic><COVID19 vaccine><Cell Body><Cells><Cellular Assay><Cellular Immune Function><Chronic><Clinical><Clinical Treatment Moab><Clinical Trials><CoV disease><Cohort Studies><Collaborations><Communicable Diseases><Concurrent Studies><Country><Development><Disease><Disease Outbreaks><Disorder><Drugs><Enteric Fever><Epitopes><Eye><Eyeball><Future><Goals><HIV Prevention><HIV Vaccine Trials Network><HIV vaccine><HIV/AIDS Vaccines><HIV/AIDS prevention><HIV/Mtb><HIV/TB><HIV/mycobacterium tuberculosis><HIV/tuberculosis><HVTN><Health><Immune><Immune Markers><Immune response><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunologic Markers><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Immunology procedure><Immunotherapeutic agent><Individual><Infection><Infection Control><Infection prevention><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Intubation><Joints><Knowledge><Laboratories><Lead><Leadership><Light><M. tuberculosis/HIV><Malaria><Measures><Mediating><Medical><Medical History><Medication><Monoclonal Antibodies><Monoclonal Antibody Therapy><Morbidity><Morbidity - disease rate><Myocarditis><NIAID><National Institute of Allergy and Infectious Disease><Outbreaks><Paludism><Participant><Pathologic><Pb element><Pericarditis><Personal Medical History><Personal Medical History Epidemiology><Persons><Peru><Pharmaceutic Preparations><Pharmaceutical Preparations><Phase><Photoradiation><Physicians><Plasmodium Infections><Play><Population><Preparation><Prevent infection><Preventative vaccine><Prevention><Preventive vaccine><Prophylactic vaccine><Prospective Studies><Protocol><Protocols documentation><Quality Control><Randomized><Randomized Clinical Trials><Reagent><Research Methodology><Research Methods><Risk><Role><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Science><Scientist><Series><Serologic><Serological><Severe acute respiratory syndrome coronavirus 2><Severity of illness><Site><Specificity><System><Testing><Typhoid><Typhoid Fever><United States><Vaccination><Vaccines><Validation><Viral Diseases><Viral Shedding><Virus><Virus Diseases><Virus Shedding><Wuhan coronavirus><adaptive immune response><adulthood><allergic/immunologic body system><allergic/immunologic organ system><cardiac inflammation><cell assay><clinical development><clinical trial analysis><cohort><corona virus disease><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><coronavirus disease 2019 vaccine><design><designing><developmental><disease duration><disease length><disease severity><drug/agent><efficacy study><efficacy trial><experience><heavy metal Pb><heavy metal lead><host response><human immunodeficiency virus vaccine><illness length><immune drugs><immune function><immune-based biomarkers><immune-based therapeutics><immunologic assay><immunologic assay/test><immunologic preparation><immunologic therapeutics><immunological biomarkers><immunological markers><immunoresponse><immunotherapeutics><immunotherapy agent><improved><interest><mAb therapy><mAbs><mortality><neutralizing mAb><neutralizing monoclonal antibodies><neutralizing vaccine><operation><pandemic><pandemic disease><prevent><preventing><programs><quality assurance><randomisation><randomization><randomly assigned><recruit><response><social role><therapeutic vaccine><treatment vaccines><vaccination study><vaccination trial><vaccine for the treatment><vaccine for treatment><vaccine study><vaccine trial><vector-based vaccine><viral infection><virology><virus infection><virus-induced disease>