Designing a T Cell Vaccine Platform
Vaccines delivered via adenoviral vectors have been shown to induce robust CD8+ T cell responses. However, there exist high levels of population immunity to human adenoviruses. Thus, we are focused on developing an adenoviral vector that induces T cell immunity, has low seroprevalence, can be delivered intranasally, and is safe and immunogenic in humans. We are currently testing multiple vaccine designs for HIV, SIV, and SARS-CoV-2 in our in-house developed adenoviral vector in murine models.
Using structure-based network analysis, we identify topologically important regions of viral proteins that are mutationally constrained. Using HLA-epitope stability assessments, we design optimal CD8+ T cell-inducing immunogens for placement inside various vaccine cassettes. We then test these vaccine designs in mice, hamsters, and non-human primates via multiple delivery modalities and assess their immunogenicity. We have designed vaccines for HIV, SARS-CoV-2, and SIV, and we are currently working on expanding our platform to include other respiratory viruses, HPV, and HCV. We are in collaborations with many pharmaceutical and biotech companies both within and outside of the greater Boston area.