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

What It Covers

Gary Nabel, CEO of MODEX Therapeutics, describes how decades of virology research at NIH and Sanofi led to a bivalent Epstein-Barr virus vaccine now in Phase 1 trials with Merck partner. The candidate targets two distinct cell-entry pathways to block both B-cell and epithelial-cell infection, potentially preventing mononucleosis, EBV-associated cancers, and autoimmune diseases including multiple sclerosis.

Key Questions Answered

• •Dual-target vaccine design: GSK's earlier EBV vaccine using only GP350 achieved 80-90% reduction in infectious mono but failed to sterilize infection because it blocked only B-cell entry. MODEX's candidate adds the GH/GL/GP42 trimer to block epithelial-cell entry simultaneously. Vaccinated animals in humanized mouse challenge studies showed sterilizing immunity, the strongest preclinical benchmark available before human trials.
• •EBV disease burden: EBV causes approximately 200,000 cancer cases annually, spanning Burkitt lymphoma, Hodgkin's disease, gastric carcinoma, and nasopharyngeal carcinoma. Beyond cancer, mounting epidemiologic evidence links latent EBV reactivation to multiple sclerosis, lupus, and rheumatoid arthritis. This positions a preventive EBV vaccine as a potential intervention against a broad cluster of chronic diseases, not merely adolescent mononucleosis.
• •Multispecific antibody rationale: Single-target antibodies allow viruses to mutate and escape. Engineering tetravalent antibodies that bind two tumor-cell antigens and two T-cell activation receptors simultaneously prevents escape while delivering a sustained T-cell killing signal directly at the tumor site. This same logic applies to MODEX's SARS antiviral candidate, which targets two viral components to suppress resistance emergence.
• •Rational vaccine design framework: When conventional killed or live-attenuated approaches fail, as with HIV and EBV, the productive path requires mapping viral glycoprotein structures at atomic resolution, identifying rare broadly neutralizing antibodies via single-cell B-cell cloning, and engineering immunogens that present only the receptor-binding domain rather than the full protein, focusing immune responses on the most vulnerable viral epitopes.
• •Phase 1 to approval pathway for EBV vaccine: With nearly 200 participants enrolled, the Phase 1 trial tests two adjuvant formulations and targets antibody titers exceeding those from natural infection. Phase 2 efficacy will measure reduction in infectious mono incidence via controlled placebo trial. Surrogate immune and genetic markers for MS and autoimmune risk allow researchers to assess broader protective effects without waiting decades for cancer or neurological endpoints.
• •Biotech spinout strategy from large pharma: Large pharmaceutical companies provide manufacturing scale but structurally deprioritize early-stage, higher-risk innovation. Nabel and Elias Zerhouni licensed the EBV vaccine and multispecific antibody platform out of Sanofi to form MODEX in 2020, then partnered with Merck through Phase 1, transferring primary clinical development responsibility to Merck while retaining collaborative scientific input. This structure lets each party contribute distinct capabilities neither could replicate alone.