Ep208: Gary Nabel on Developing a Vaccine for Epstein-Barr Virus

Gary Nabel traces his scientific journey from his undergraduate years at Harvard Medical School through his MD-PhD training, influenced by his government advisor who suggested he pursue science to ultimately work in policy. His early career was shaped by mentorship from David Baltimore at Caltech, where he studied the intersection of viral biology and immunology, publishing foundational work on HIV activation in T cells via the NF-kappaB transcription factor in 1987.

Nabel's early career spanned academic medicine at the University of Michigan, where he balanced clinical practice with laboratory research, then transitioned to the NIH where he founded and directed the Vaccine Research Center (established by President Clinton in 1998). At the VRC, he led development of rational vaccine design approaches for HIV and other pathogens including Ebola, avian flu, and SARS-CoV-2. Key technological advances enabling this work included structural biology methods that revealed viral glycoprotein structures at atomic resolution, improved B cell antibody identification techniques, and advances in DNA and mRNA vaccine platforms.

Nabel moved to Sanofi as Chief Scientific Officer in 2012, where he oversaw R&D portfolios and established the Breakthrough Laboratories—a skunkworks division pursuing novel approaches to antibody engineering. There, he and colleague Elias Zerhouni developed multi-specific antibodies that could simultaneously target multiple antigens, addressing the challenge that single-target approaches fail against viruses that readily mutate to escape immune responses. The team also expanded earlier work on Epstein-Barr virus vaccines using nanoparticle scaffolds to present multiple viral antigens.

Nabel explains that the GSK EBV vaccine trial (GP350-based) showed 80-90% reduction in infectious mononucleosis but failed to completely prevent viral replication in some subjects. Through subsequent research, Nabel's team identified that the virus uses two distinct cell entry pathways—B cells via GP350 and epithelial cells via a GH-GL-GP42 trimer complex—requiring a bivalent vaccine targeting both pathways. This led to founding Modex Therapeutics in 2020 to develop and advance this technology.

Modex partnered with Merck, leveraging Merck's HPV vaccine experience and manufacturing capabilities while Modex contributed scientific innovation and speed. The EBV vaccine candidate (bivalent) is now in phase one trials with approximately 200 enrolled subjects. Preclinical studies in mice and non-human primates demonstrated high-titer neutralizing antibodies and sterilizing immunity in humanized mouse models. Beyond the EBV vaccine, Modex has five phase one programs including a tetravalent anti-SARS antibody, three tetravalent cancer immunotherapy candidates targeting tumor cells and T cells simultaneously, and an immune rejuvenator targeting T cell activation pathways.