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Principal Investigator: Michael S Diamond
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2022
Award: $7,990,794
Funding agency: National Institute of Allergy and Infectious Diseases
Overall Summary
Given the historical outbreaks of coronaviruses, coupled with the recent emergence of SARS-
CoV-2 and the destabilizing consequence of COVID-19 on global health and economy, there is
an urgent and critical need to develop new vaccines capable of broad protection against existing
and future Sarbecoviruses and Merbecoviruses. This P01 program project (PPG) addresses
the hypothesis that a combination of evolutionarily-designed and optimized B and T cell
antigens can confer broad and protective immunity against Sarbecoviruses and
Merbecoviruses that currently exist or could emerge from zoonotic reservoirs. The PPG
integrates the work of eleven leading laboratories with records of collaboration that have expertise
in coronavirus biology, viral pathogenesis, B and T cell immunity, vaccine development, animal
challenge studies, structural biology, antibody structure and function, antigen design, and
evolutionary analysis of viruses. All Projects and Cores plan interactive studies with the focused
goal of designing optimized B and T cell antigens for incorporation in adenoviral (ChAd) and
vesicular stomatitis virus (VSV) vectors to create mucosal and systemic vaccines that protect
against infection and disease caused by a range of coronaviruses of potential concern. The PPG
is served by a central Animal Challenge Core that performs vaccination and infection
experiments in mice and hamsters and a central Administrative Core that streamlines data
management and sharing, provides computational analysis for down-selection and scientific
decision-making, and facilitates communication. Our proposal and antigen design program serves
as a blueprint for possible product development with ChAd vaccines, VSV-based vaccines, or
even with other platforms (e.g., mRNA vaccines, nanoparticles, etc.) not directly evaluated here.
By the conclusion of our PPG, we envision generating at least one and likely multiple viral-
vectored vaccine platforms that induce broad spectrum immunity to multiple coronaviruses of
concern including human and zoonotic Sarbecoviruses and Merbecoviruses that could emerge in
the future.
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syndrome related corona virus 2><Site><Source><Speed><Structural Biologist><Structure><T cell response><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><T8 Cells><T8 Lymphocytes><Tissues><VSV><Vaccination><Vaccine Design><Vaccines><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Viral Pathogenesis><Viral Vaccines><Viral Vector><Virus><Work><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><adeno vector><adenovector><aminoacid><base><beta CoV><beta coronavirus><betaCoV><betacoronavirus><catalog><computational analyses><computational analysis><computer analyses><corona virus><corona virus disease 2019><corona virus emergence><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 impact><coronavirus disease-19 virus><coronavirus emergence><coronavirus infectious disease-19><coronavirus 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