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.
 
Our efforts fall into the 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 antibodies with conditional activity at the site of disease and antibodies that resist pathogen efforts to evade capture
    • 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, Curr Opin Chem Eng19: 131-141 (2018). [link]
 
  • Vaccines that outsmart pathogens: Using what we learn from antibodies that prevent disease, especially antibodies that protect despite a pathogen's efforts to evade the immune system, we aim to design vaccine antigens that induce potently protective antibody responses. 
    • Goldsmith J, DiVenere AM, Maynard JA, McLellan JS. Structural basis for antibody binding to adenylate cyclase toxin reveals RTX-linkers as key neutralization-sensitive epitopes. Plos Pathogens 17(9): e1009920 (2021). [link]
  • T cell-based therapeutics: 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. J Biol Chem, 294: 5790 (2019) - [link].