HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals

This proposal outlines the scientific agenda for the Leadership and Operations Center of the HIV VaccineTrials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4continents 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 clinicaldevelopment trials and currently has 2 vector based vaccines (ALVAC and Ad26) and 1 broadly neutralizingmonoclonal 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 thefield 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 thisinformation in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study wepropose initiating an observational cohort study of approximately 400 persons in the United States (22 trialssites) and Peru (5 sites) convalescing from SARS-CoV-2 infection. Participants will be recruited from a varietyof risk groups and clinical cohorts: hospitalized vs. non-hospitalized, symptomatic vs. asymptomatic, adultsbetween 18 and 55 years of age and those older than 55 years, and persons with high interest clinical orvirologic presentations (eg, persons who developed myocarditis/pericarditis, required intubation, had prolongedviral shedding, or who develop a positive virologic test after initially clearing the infection). Specific aims ofthis study include identifying serologic reactivities that differentiate SARS-CoV-2 infection from vaccination, todevelop and qualify a suite of immunologic assays and reference reagents that will permit detailedinterrogations of the immune response to infection, to measure SARS-CoV-2 adaptive response in keypopulations 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 infectedand recovered from SARS-CoV-2 and will shed light on the role the immune system plays in successfullyclearance of infection. It will improve our understanding of the dynamics and duration of responses, as well asthe epitope specificity and other defining signatures, and will inform rational design and testing of preventiveand therapeutic vaccines and monoclonal antibodies. In addition, this protocol will lay the groundwork forprospective studies of this infection, better defining key risk groups and knowledge gaps. Lastly, this study willprepare 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 ofnetwork machinery as the HVTN prepare to roll-out several efficacy trials as part of the joint NIAID COVIDPrevention Network in coming months.