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

Episode Summary

Executive Summary: Gary Nabel traces his path from virology and immunology research to biotech leadership, explaining how advances in structural biology, antibody engineering, and genomics enabled Modex Therapeutics to pursue multi-specific biologics. The centerpiece is an EBV vaccine designed to block infection in both B cells and epithelial cells, with Merck as partner and phase 1 underway, alongside cancer and antiviral programs.

Main Topics: Nabel’s scientific career and mentor influence (Priority: 5/5): Nabel describes growing up in New England, choosing science over government, and being shaped most by David Baltimore’s mentorship, which led him into virology and immune system research. Why vaccines and translational medicine mattered (Priority: 5/5): He explains that the goal of his career was to bridge lab science and patient benefit, using vaccines as an ideal way to convert basic discoveries into public health impact. The Vaccine Research Center and rational vaccine design (Priority: 5/5): Nabel recounts founding the NIH Vaccine Research Center to apply emerging tools to HIV and other threats, emphasizing structural biology, B-cell biology, sequencing, and recombinant technologies. Sanofi era and breakthrough antibody engineering (Priority: 4/5): At Sanofi, he ran a small “breakthrough lab” to pursue disruptive ideas, including multi-specific antibodies and nanoparticle vaccine platforms, benefiting from advances in antibody discovery and manufacturability. Epstein-Barr virus as a major unmet need (Priority: 5/5): He details EBV’s role in mononucleosis, cancers, and autoimmune disease, arguing that a vaccine could prevent not only acute illness but also downstream chronic disease burden. Modex Therapeutics and the Merck partnership (Priority: 5/5): Nabel explains why he co-founded Modex to support early, creative biologics development and why Merck was an ideal partner for advancing the EBV vaccine through clinical development. Broader Modex pipeline beyond EBV (Priority: 4/5): He closes by outlining other phase 1 assets: an anti-SARS multispecific, three cancer-targeting tetravalent molecules, and an immune rejuvenator aimed at activating T cells.

Key Arguments: Modern vaccines require rational design rather than older whole-virus approaches when pathogens like HIV and EBV evade immunity through complexity or mutation. Structural biology, single-cell/B-cell cloning, sequencing, and recombinant DNA made it possible to identify vulnerabilities and engineer precise biologics. Multi-specific antibodies are a logical response to viral escape and cancer resistance because they can hit multiple targets in one molecule. EBV is not just a mononucleosis virus; it is implicated in roughly 200,000 cancers annually and likely in multiple sclerosis and other autoimmune diseases, making prevention especially valuable. The EBV vaccine must block both B-cell and epithelial-cell entry, because prior single-target approaches likely missed a key route of infection. Biotech startups are better suited than big pharma for early, risky, creative platform work, while large partners like Merck are better for scale and late-stage development. Clinical success can be measured initially by safety and immunogenicity, then by reduction in infectious mononucleosis and, over time, surrogate markers linked to cancer and autoimmune disease risk.

Data Points: Year of birth and DNA structure discovery: Same year - Nabel notes that he was born the year the DNA structure was solved, framing his career as part of biology’s “golden age.” Nature paper on HIV activation: 1987 - He says his first major paper from David Baltimore’s lab identified NF-kappa-B involvement in HIV activation in T cells. Vaccine Research Center announcement: 1998 - Nabel says President Clinton announced plans for an NIH Vaccine Research Center in a 1998 speech. Sanofi tenure: 2012 to 2020 - He describes serving as CSO at Sanofi for roughly eight years before founding Modex Therapeutics. EBV-associated cancers annually: ~200,000 cases per year - Nabel cites the estimated global burden of cancers linked to EBV infection. Mono reduction in GSK EBV vaccine trial: ~80% to 90% reduction - He references an earlier GSK trial targeting GP350 that substantially lowered infectious mononucleosis incidence. Modex phase 1 enrollment: Close to 200 patients - He says the Merck-partnered EBV vaccine program has enrolled nearly 200 participants in phase 1. Modex pipeline assets in phase 1: 5 products - He states Modex currently has five phase 1 programs. Cancer-directed multispecifics in phase 1: 3 programs - He says three of the five phase 1 products are tetravalent antibodies targeting cancer cells and T cells. Targets in EBV vaccine: 2 viral entry pathways - He explains the vaccine combines truncated GP350 and the GH/GL/GP42 trimer to block B-cell and epithelial-cell entry.

Pivotal Quotes: "“If you go into science, you’ll be able to work in government and be able to use that as a tool.”" — Gary Nabel: He recounts the advice that helped steer him from government studies into a science career with public-service impact. "“The best way to contain them is by making a vaccine.”" — Gary Nabel: He explains the motivation behind the NIH Vaccine Research Center, especially in the context of HIV and other viral threats. "“The only way we’ll ever do this is by creating a company.”" — Gary Nabel: He describes the reasoning behind co-founding Modex Therapeutics to advance creative multi-specific and EBV vaccine programs.

Implications: The episode argues that next-generation vaccines and multispecific biologics can prevent not just infections but also cancers and autoimmune disease. If Modex succeeds, it could validate a platform approach to high-value infectious disease and immunotherapy development.