Steven L. Zeichner, MD, PhD

Our lab has worked in several areas involving viral pathogenesis, host responses to infection, understanding immunogenicity, the control of viral gene expression and viral latency, and vaccine development. Recently, the lab has been developing a new, rapid, ultra low-cost, globally appropriate, synthetic biology-informed vaccine platform: Killed Whole Cell (KWC) Genome-Reduced Bacteria (GRB) in which vaccine antigens are placed on the surfaces of the bacteria via an inducible Gram-negative autotransporter in an expression plasmid that we synthesized. In the platform, DNAs encoding an antigen are synthesized and cloned into the expression plasmid in ~2 weeks for ~$50/construct, enabling creation of a testable vaccine in ~3 weeks from antigen selection. The platform is ideal for rapid pandemic/biothreat response and custom therapeutic cancer vaccines. We published an initial implementation of the platform for a universal coronavirus vaccine that can protect against clinical disease in a pig model (Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2025622118. doi: 10.1073/pnas.2025622118). We have published additional descriptions outlining how our platform can be used to design new antigens with improved immunogenicity (Vaccines 2026, 14(1), 14; https://doi.org/10.3390/vaccines14010014). Conventional KWC vaccines are a long-established technology. Approved KWC vaccines exist for many human and animal diseases. KWC bacterial vaccines are stable at 2-6 C for 2 years. KWC vaccines can be produced in existing factories around the world using abundant starting materials. We believe that our new vaccine platform will have a transformative benefit for human and animal health. We have also recently been studying the pathogenesis of COVID-19, investigating our new hypothesis that some antibodies elicited by SARS-CoV-2 may have enzymatic activity (“abzymes”) that may mediate some of the unusual features of COVID-19 and associated diseases like Long COVID. We published an initial description of the work (mBio 15:e00541-24. doi: 10.1128/mbio.00541-24) and are now exploring additional implications of the hypothesis, and have showed that convalescent patients also make abzymes and that the abzyme activity correlates with clinical disease features (mBio 16:e01735-25doi/10.1128/mbio.01735-25). While much work remains to be done, if SARS-CoV-2 abzymes play an important role in the pathogenesis of COVID-19 and associated diseases, the findings can inform future therapeutic developments that target the underlying causes of disease, in contrast to current therapies, which are largely directly at managing or mitigating symptoms.