COVID-19 is an emerging focus for EpicentRx, a private biotech focused on multiple immune-mediated disorders. The La Jolla, California–based company is developing a next-gen COVID vaccine for SARS-CoV-2 based on nucleocapsid rather than spike protein.
The recombinant replication-competent adenoviral vaccine that expresses the SARS-CoV-2 nucleocapsid protein could be more resistant to COVID-19 variants.
The real-world effectiveness of spike-protein-based COVID-19 vaccines has generally dipped since their integration as a wave of SARS-CoV-2 variants has emerged.
But while the spike protein mutates frequently, nucleocapsid doesn’t.
“The RNA for the virus is wrapped around it,” said EpicentRx CEO Dr. Tony Reid. “If it mutates and alters its three-dimensional structure very much, the RNA will unwind, and the virus will be nonviable.”
EpicentRx plans to work with partners to take a nucleocapsid-based next-gen COVID-19 vaccine candidate into clinical trials.
Dr. Tony Reid
“We’ve had some good discussions with pharmaceutical companies as well as some of the government agencies,” Reid said. “We’ve made a GMP manufacturing batch ready for clinical testing.”
Nucleocapsid is a relatively large protein with multiple T-cell epitopes associated with it. An epitope is part of an antigen the immune system recognizes.
“If we generate a T-cell response against nucleocapsid, it would augment any spike vaccines that came along,” Reid said.
A vaccine based on the invariant nucleocapsid protein also could yield a T-cell activation that results in a long-term immune response.
Earlier this month, International Journal of Infectious Diseases published a commentary on the need for a next-gen COVID-19 vaccine candidate based on nucleocapsid. Reid was a co-author.
Primarily focused on cancer vaccines, EpicentRx has substantial experience giving vaccines to immunosuppressed cancer patients.
Reid notes that early reports describing immunosuppressed patients infected with COVID-19 found their bodies served as dangerous breeding grounds for the virus. “Such patients would generate a polyclonal immune response, but their T cell response was not robust, and there was residual viremia.”
As a result, new variants emerged that could resist or escape antibodies.
The situation has led to diminished effectiveness of COVID-19 vaccines and antibodies.
“It made absolute sense that Pfizer, Moderna and other companies went after the spike protein,” Reid said, as vaccines that effectively target the spike protein can yield strong protection.
But because the spike protein frequently mutates, developing a current vaccine that targets the latest circulating variants remains challenging. “You’re just chasing your tail,” Reid said.
The development of mRNA-based vaccines during the pandemic was unprecedented. “When the original mRNA vaccines came forward, it was a new technology,” Reid said. “No one knew that it would work.”
It shook the field when Phase 3 studies of the vaccines showed they offered greater than 90% efficacy. “Many people thought, ‘COVID is done,’” Reid said.
But now, the virus is still spreading infections throughout the world. “I still think the spike vaccines should be around, but combining them or augmenting them with nucleocapsid would be beneficial,” Reid said. “We particularly think that it will be helpful because many of the problems we’re seeing now are long-term organ toxicities. So a T-cell response that can eradicate the virus from infected cells is going to be, we think, a major benefit of nucleocapsid technology.”
EpicentRx also has a Phase 1 study for the treatment of cancer. The centerpiece of that study is AdAPT-001, which carries a gene that traps or neutralizes a protein known as transforming growth factor-beta (TGF-beta).