Viral Pathogenesis Laboratory

Barney Graham, M.D., Ph.D., Chief

The goal of the Viral Pathogenesis Laboratory (VPL) in the Vaccine Research Center (VRC) is to better understand basic aspects of viral pathogenesis and apply that knowledge toward development of safer and more effective vaccines. Many aspects of prior VPL work were instrumental in the rapid response to the COVID-19 pandemic. Under Dr. Graham's direction, the VPL designed and developed the first COVID-19 vaccine candidate and helped discover the first SARS-CoV-2 neutralizing monoclonal antibody to enter human clinical trials. This was achieved by implementing a plan outlined for rapid pandemic response, based on prototype pathogen preparedness. Guided by structures of HKU1-CoV, MERS-CoV, and SARS-CoV combined with a generalizable spike antigen design solution established for betacoronaviruses, technological tools developed by the VRC for precision vaccinology, and rapid platform manufacturing in collaboration with Moderna, Inc., the first clinical trial participant was injected with a candidate mRNA vaccine expressing stabilized SARS-CoV-2 spike protein 65 days from the time of sequence release. Preclinical testing and assay development were performed in parallel to support advanced clinical trials for mRNA-1273. The VPL's prior work on the pathogenesis of respiratory syncytial virus (RSV) vaccine-associated enhanced respiratory disease (VAERD) also provided an essential framework for safety evaluations and regulatory decisions required for accelerated vaccine development (Graham, Science 2020). To define how coronaviruses and other viruses cause disease, the VPL investigates functional and structural features of viral pathogens as well as mechanisms for regulating the composition and timing of host immune responses using in vitro systems, animal models, and clinical trials. Understanding RSV biology and pathogenesis has been a central theme of the VPL. The VPL emphasizes the use of new technologies that have evolved over the last decade driven largely from efforts to develop an HIV vaccine. Some of these include structure-based antigen design, self-assembling nanoparticle display, single-cell analysis for assessing T cell function and discovering monoclonal antibodies, defining antibody repertoires and lineages, and nucleic acid and vector-based vaccine antigen delivery vehicles.

View all research conducted at the Vaccine Research Center (VRC)

Major Project Areas

  • Vaccine and monoclonal antibody development for COVID-19, RSV, influenza, EV-D68, Nipah, Zika, HIV, Ebola, and other viral emerging pathogens
  • Structure-based vaccine design and structural basis for antibody-mediated virus neutralization
  • Role of functional hierarchy and regulation of T-cell responses in immunity and pathogenesis of viral diseases
  • Prototype pathogen approach for pandemic preparedness and response

People

The Viral Pathogenesis Laboratory includes the following principal investigators, staff scientists, and/or staff clinicians:

Sections and Units

The Viral Pathogenesis Laboratory includes the following sections and cores:

Content last reviewed on