EpicentRx Inc. (“EpicentRx”), a late-stage biopharmaceutical company developing platforms that treat and target multiple immune-mediated disorders, has published a commentary in one of the top infectious disease journals, International Journal of Infectious Disease (IJID), emphasizing the importance of a “universal” coronavirus vaccine based on the nucleocapsid or N protein instead of the spike or S protein, which is used in current COVID vaccines. The commentary is authored by Bryan Oronsky, Chris Larson, Scott Caroen, Farah Hedjran, Ana Sanchez, and Tony Reid, all of EpicentRx. (click on link to read: IJID nucleocapsid commentary).
The authors point to the N-protein, as an internal RNA-binding protein, as being more essential to viral survival than the S protein, and much more stable and less likely to mutate. Based on this fact, the authors contend that an N-based vaccine would be useful not only against the new COVID-19 variants that continue to appear with regularity but also possibly against all coronaviruses, present or future, since nucleocapsid is a highly conserved or shared coronavirus protein with the potential to establish broad protective immunity.
According to viral immunologist and EpicentRx CEO, Dr. Tony R. Reid, “We’ve already faced three coronavirus pandemics, starting with SARS CoV-1, then MERS, and now SARS-CoV-2 or COVID-19. There have been reports of potential future pandemics due to new variants, which means we need to be ready for the ever-present possibility of ongoing mutation of the virus, especially within the spike protein, as the virus circulates in the population, or the potential for future transmission from animals to humans. If you look at the first SARS-CoV-1 patients, even now they still have T-cells, which recognize the SARS N-protein, and this potentially immunizes them against other coronaviruses. That’s why we made a nucleocapsid targeting vaccine.”
This vaccine was developed from EpicentRx’s adenovirus vaccine platform called AdAPT. The adenovirus, an agent of the common cold, has been modified to carry different genes, which in the case of the EpicentRx vaccine, is nucleocapsid. When the vaccine is injected, it makes many copies of itself, and the nucleocapsid gene that it carries, in the capacity of a “biologic factory” for high level production of nucleocapsid inside the body. The first AdAPT clinical candidate and immediate predecessor of this vaccine is called AdAPT-001, currently in a Phase 1 trial for the treatment of cancer (BETA PRIME; ClinicalTrials.gov Identifier: NCT04673942). AdAPT-001 carries a gene that traps or neutralizes a protein called transforming growth factor-beta (TGF-beta), which helps tumors to grow.
The EpicentRx vaccine was made “in house” at its own Good Manufacturing Practice (GMP) Production Facility, which is a departure from the usual pharmaceutical model of outsourcing contract manufacturing to third party companies. Based on its experience with AdAPT-001, EpicentRx moved rapidly on design and manufacture of the vaccine for a Phase 1 clinical trial. As Dr. Reid explained, “This is the time for chess, not checkers. If we don’t plan ahead, we’ll be chasing this virus from behind”.