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Smith Research

Scott A. Smith MD PhD

PRIMARY APPOINTMENT:

Associate Professor of Medicine

CONTACT:

UVA Division of Asthma, Allergy, and Clinical Immunology
PO Box 801355
MR-4
Charlottesville, VA

EDUCATION AND TRAINING

  • Bachelor of Science in Biology, Pre-Medicine
    California University of Pennsylvania
    California, PA
  • PhD in Microbiology and Immunology, 2002 “Structure and Function Studies of the Vaccinia Virus Complement Control
    Protein.” Mentor Girish J. Kotwal
    University of Louisville, School of Medicine, Department of
    Microbiology and Immunology
    Louisville, KY
  • Doctor of Medicine
    University of Louisville, School of Medicine
    Louisville, KY MD

Post Graduate Training

  • Residency in Internal Medicine
    Vanderbilt University Hospital
    Nashville, TN Medicine
  • Fellowship in Infectious Diseases
    Division of Infectious Diseases
    Vanderbilt University Hospital
    Nashville, TN Medicine

RESEARCH SUMMARY

Analogous to work in viral infectious diseases, our work in the field of allergic diseases has several translational goals. The first approach is to directly map the human IgE allergic antibody response, aiming to generate switched variant IgG blocking therapeutics that mitigate anaphylaxis due to accidental exposure. Like identifying neutralizing epitopes, developing blocking therapeutics requires first the mapping of immunodominant pathogenic IgE antibody responses to find those antibodies that would be most effective at functionally blocking anaphylaxis. We have pursued this goal on multiple fronts and have only begun to publish the results, with our peanut IgE work currently in press at the Journal of Allergy and Clinical Immunology. This work is patented, licensed, and currently in therapeutic development.

A second translational goal of our current work is to design hypoallergenic immunotherapeutics. This concept is analogous to using neutralizing human antibodies to create vaccines that elicit immune responses yielding similar antibodies rationally. We use the pathogenic IgE molecule, in collaboration with various structural biology groups, to molecularly define the IgE epitope on key major allergen proteins. These epitopes are then rationally mutated to create hypoallergens (allergen proteins with less IgE binding competence), without alteration of their structure and preserving all other antibody epitopes. These engineered vaccine molecules are highly effective in our murine model at abrogating IgE binding and anaphylaxis induction. We have only begun patenting and publishing this work, with several manuscripts in preparation and one published in PNAS Nexus.

Finally, our third active translational goal is to develop parasite vaccines. Despite it being common knowledge that the IgE antibody response protects us from helminth infections, nothing is known about the antigens or mechanisms of protection. To begin developing novel vaccine strategies to combat helminth infection, we have identified and characterized those immunodominant antigens responsible for profound induction of IgE antibody responses. Patenting is underway, and these initial results are published in the Journal of Allergy and Clinical Immunology. We are actively characterizing these responses in our murine model, using both active and passive protection against infection with the Brugia malayi helminth. Similarly, we have recently begun work with ectoparasites, ticks. It is not widely known that mammals can gain immunity to tick bites, a phenomenon called acquired tick resistance. This immunity is dependent on IgE and basophils. Still, it is otherwise completely unknown. We are expanding a panel of human IgE antibodies from individuals with alpha-gal syndrome, a tick-borne allergic disease, and those who have frequent and recurrent tick bites. Our goal, similar to that with helminths, is to utilize the human IgE antibody response to identify immunodominant antigens and rationally design vaccines that induce active immunity in naive humans.

I plan to continue this translational human B cell research toward the development of antibody therapeutics and the rational design of novel vaccines and immunotherapies. We will develop IgG blocking therapeutics to mitigate against anaphylaxis, use structure-based design to create novel hypoallergenic immunotherapeutics, and continue work on parasite vaccines, developing vaccines based on IgE antibody-antigen discovery.