The overarching mission of our research program is to improve global public health. We translate insights from productive adaptive immunity into effective vaccines and diagnostics for infectious diseases. Our vaccine platform uses engineered T cell-inducing immunogens as probes to measure and understand cellular responses to infection and/or vaccination in a variety of cohorts or mouse models. In collaboration with biotech companies, we then test these vaccines in small animal models to assess their safety and efficacy. Our rapid diagnostic platforms use 1) monoclonal antibodies derived from mice or humans to detect pathogen antigens or 2) novel recombinase enzymes, along with polymerase, to isothermally amplify pathogen nucleic acids.

We synthetically design viral epitopes or proteins that are predicted to be preferentially targeted by the human cellular response. We fuse these epitopes or proteins to a non-infectious bacterial toxin that delivers these protein cargoes into the cell to induce CD4+ and CD8+ T cell responses. We use these “immunogens” to characterize the human or murine T cell responses during infection and/or vaccination in cohort studies in the United States and in the global south (e.g., West Africa, LATAM) or in the lab. In particular, we are interested in understanding differences in the T cell response during asymptomatic infection as compared to those that are mounted during severe disease. Separately, we profile human and murine pathogen-specific antibodies to define the specific features that track with protection, with implications for their potential use as therapeutics.

Vaccinology:
Once an optimal immunogen has been identified, we use it as a vaccine in small animal models to test for safety, immunogenicity, and efficacy. We and our biotech partners have developed vaccines for SARS-CoV-2, flaviviruses, Ebola, and HIV, and we are currently working to expand our platform to include other viruses of pandemic potential.

Biotech company: Mir Biosciences, Inc. (www.mirbio.science) was launched to bring these innovative immunogen-based products to market and to empower researchers in designing their own T cell immunogens. Mir Bio aims to accelerate the development of next-generation vaccines and diagnostics for a variety of (infectious) diseases.

Antigen-based rapid tests:
We develop monoclonal antibodies by immunizing mice with Fc-tagged viral antigens, or recruiting exposed patients. We then single cell sort B cells specific to pathogen-specific antigens, then sequence and clone heavy and light chains for expression and purification of monoclonal antibodies. Purified monoclonal antibodies undergo systematic screening using several molecular biological and biochemical methods. We then use the high avidity monoclonal antibodies along with nanoparticles to develop low-cost, rapid diagnostics for testing in the lab and in cohort studies.

Recombinase polymerase amplification (RPA)-based rapid tests:
We recently identified novel recombinase enzymes, which in conjunction with polymerase and a single set of pathogen-specific primers, can rapidly (>10 minutes) amplify nucleic acids isothermally (e.g., at a single ambient temperature, typically between 30-42°C). By reconfiguring the primers with tags and the use of amplicon-specific probes, we can visualize diagnostic results via lateral flow chromatography. We can also sequence the RPA amplicons, enabling us to perform molecular epidemiology of infectious diseases.