Outer membrane vesicle biogenesis and vaccine development
Recent advances in nanoscale engineering have created a new class of particulate bionanotechnology that uses biomimicry to better integrate vaccine adjuvants and antigens. These pathogen-like particles, or PLPs, can come from a variety of sources, ranging from fully synthetic platforms to biologically-derived, self-assembling systems. Outer membrane vesicles (OMVs) derived from gram-negative bacteria demonstrate great promise as a next-generation vaccine platform. OMVs have the potential to seamlessly combine the biomimicry of virus-like particles with flexible, heterologous antigen integration and broad bacterial self-adjuvanticity. By employing molecularly engineered targeting and stimulation of key immune cells, we have pioneered the development of recombinant OMVs as a vaccine delivery platform and used the resulting engineered OMVs against high-impact, unsolved vaccine targets including bacterial pathogens, viruses, and human cancers.
Notable contributions include:
(i) seminal demonstration that bioengineered OMVs derived from non-pathogenic E. coli (J Mol Biol 2008) represent a promising avenue for stimulating robust antibody responses towards desired antigens (PNAS 2010)
(ii) first demonstration of OMVs as a means of polarizing immune responses towards Th1 or Th2 responses (PLoS ONE 2014) and leveraged biased OMVs to protect against lethal doses of influenza (Vaccine 2016; Mol Ther 2017)
(iii) devised a controlled release OMV formulation that offers an effective single-dose, long lasting and rapidly effective vaccine to protect against influenza (Vaccine 2017)
(iv) invented novel strategies for remodeling the exterior of OMVs with designer glycan structures including pathogen-mimetic oligosaccharides (PNAS 2016; PNAS 2018) and tumor-associated carbohydrate antigens (Cell Chem Biol 2016) that elicited class-switched IgG antibodies with specificity for glycans of interest