With apologies to Toy Story’s Buzz Lightyear for borrowing his “To Infinity and Beyond” catchphrase, EpicentRx has developed and manufactured a Nucleocapsid vaccine, N-finity or N-VAX, for COVID-19, which has the potential to universally protect against all current and future coronavirus strains. This hope is based on the importance of the nucleocapsid (N) protein to all coronaviruses since it specifically binds to, wraps around, and stabilizes the genomic RNA of the virus. Moreover, unlike the highly mutable Spike protein, around which the current crop of vaccines is based, the nucleocapsid gene is highly conserved and stable, which, in theory, makes N-finity more variant resistant.
CEO of EpicentRx, Dr. Tony Reid, and one-half of the brain trust behind the development of N-finity, talked to the pharmacology-based electronic magazine, Drug Development & Delivery (DDD) about the possibilities this new approach may present to the healthcare community. The interview write-up, entitled “A next-gen vaccine that could help end COVID-19 whack-a-mole,” by Brian Buntz, is clickable here.
N-finity is based on EpicentRx’s platform of AdAPTTM self-amplifying adenoviruses, which have been modified to not target healthy tissues and to express high levels of the genes that they carry, which in the case of N-finity, is Nucleocapsid. AdAPT-001, the lead virus in EpicentRx’s AdAPT platform, is in a Phase 1/2 clinical trial for the treatment of cancer. It carries and overamplifies a protein called a transforming growth factor-beta (TGF-beta) trap. This trap binds to and neutralizes TGF-beta, which cancers overexpress to protect themselves against attack from the immune system.
The main takeaways from Dr. Reid’s interview are that while neutralizing antibodies safeguards against COVID infection, it is the T cell immune response that protects in the setting of low or waning antibody levels and that is essential for viral clearance. The nucleocapsid contains many thousands of epitopes or protein fragments that T cells recognize and that several coronaviruses share, which makes it an excellent candidate around which to base a universal or pan-coronavirus vaccine, as EpicentRx has done with N-finity. Also, contrary to the pervasive belief that COVID is finished, and that life goes on, antibody-resistant variants continue to emerge with alarming frequency, which is a particular threat to immunosuppressed cancer patients that are unable to mount a vigorous T cell response. Another potential benefit of N-finity is protection against long COVID because of “a T-cell response that can eradicate the virus from infected cells,” according to Dr. Reid.
Before SARS-CoV-2 was SARS-associated coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). The N-finity vaccine has been given the green light by the FDA for clinical trials. Ideally, it will go “viral” before the fourth —and Dr. Reid might say inevitable—coronavirus outbreak.
