RESEARCH GOALS

We strive to develop protein therapeutics and vaccines to address unmet medical needs in infectious diseases, with a focus on Bordetella pertussis and cytomegalovirus as target pathogens. These proteins aim to directly interfere in disease progression or augment essential immune system activities. This work involves design of proteins with therapeutic potential, production in recombinant expression systems, biophysical and biochemical analyses to elucidate the molecular basis of activity and, ultimately, in vitro and in vivo experiments to evaluate a protein's therapeutic potential in the context of a complex organism.
 
These efforts fall into three general categories described below.  In addition, we develop tools to support our engineering efforts, such as our recently described mammalian display system that supports engineering of proteins requiring mammalian membrane, post-translational modifications or other features specific to  mammalian cells to produce active protein. 

 

  • Advanced antibody therapeutics: Discovery and design of antibodies endowed with novel capabilities, such as the ability to preferentially localize at the site of disease and pathogen-resistant antibodies able to evade microbial escape mechanisms. 
    • Nguyen AW, DiVenere AM, Papin JA, Connelly S, Kaleko M and Maynard JA, Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons. Science Advances 6, eaay9258 (2020).​ [link]
    • Wagner EK and Maynard JA. Engineering therapeutic antibodies to combat infectious diseases, Current Opinion in Chemical Engineering19: 131-141 (2018). [link]
 
  • Design of vaccine antigens: Understand mechanisms of protective immunity to Bordetella pertussis, focusing on the pertussis toxin and the adenylate cyclase toxin, and use this information to engineer more effective vaccines and therapeutics.
    • Wang X, Gray MC, Hewlett EL  and Maynard JA*.  The Bordetella Adenylate Cyclase Toxin RTX Domain is Immunodominant and Elicits Neutralizing Antibodies. Journal of Biological Chemistry  290(6): 3576-91 (2015). [link]
  • T cell based therapeutics: Harness and redirect cellular immune responses towards virally-infected cells through manipulation of T cell receptor-peptide MHC interactions.
    • Human cytomegalovirus-specific T cell receptor engineered for high affinity and soluble expression using mammalian cell display. Journal of Biological Chemistry, 294: 5790 (2019) - [link].

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