The research in my laboratory focuses on the development of synthetic and chemically-defined vaccines for eliciting antibody- and cell-mediated immunity against solid cancers and infectious diseases. In contrast to live-attenuated vaccines, the development of synthetic vaccines is based on (1) understanding the immunobiology of infection and identification of specific target molecules and (2) the development of an appropriate vaccine delivery system to elicit the right kind of immune response. We utilize molecular self-assembly to generate modular and multivalent constructs (nanofibers, nanoparticles, vesicles etc.), where each construct is composed of a non-immunogenic self-assembling subunit covalently linked to an adjuvant, immunogen, or immunotherapeutic molecule. Our goal is to engineer the vaccine construct to be self-adjuvanting, deliver antigens/therapeutics through specific pathways, and polarize immune responses for the optimal expression of B and T cell effector function and the differentiation and maintenance of antigen-specific memory CD4+ and CD8+ T cells. While this technology is broadly useful, we are currently focusing its development on two critical areas: immunotherapy for solid tumors and prevention of chronic infectious diseases such as malaria.
We are also interested in the development of multiepitope vaccines, for example where the epitopes mediate HLA-restricted protection against a range of antigens or correspond to multiple HLA super type families to establish a broad population coverage. The highly modular nature of the self-assembling platform allows for incorporating epitopes derived from multiple pathogens or strains of a particular pathogen to elicit broadly neutralizing immune responses. Additionally we are interested in developing and discovering immunomodulatory materials that interact with specific pathogen pattern receptors of the innate immune system and utilizing these materials to shape the adaptive immune response. Ultimately we aim to develop totally synthetic, chemically defined, multivalent vaccines for the treatment and prevention of intractable diseases that cannot be addressed using conventional methods of vaccination.