In March 2020, while most people around the world were working or studying from home as the COVID-19 pandemic shut down communities, City of Hope scientist Don J. Diamond, Ph.D., and team kept working — masked and keeping a safe distance from each other — determined to develop a better COVID-19 vaccine than what was being touted as a superior product.
Their efforts paid off. Within six months, the team developed COH04S1, a COVID-19 investigational vaccine that has a unique dual-antigen design. It also used a platform, or delivery system, designed by a City of Hope research team within Diamond’s laboratory.
Remarkably, in less than a year, the vaccine was in a Phase 1 clinical trial at City of Hope.
Then, in November 2021, GeoVax, Inc., a biotechnology company, licensed COH04S1 to further develop and commercialize the vaccine. So far, the vaccine — now called GEO-CM04S1 — has been in three clinical trials to test its safety and effectiveness.
Now, Dr. Diamond, a professor in City of Hope’s Department of Hematology and Hematopoietic Cell Transplantation, and team are celebrating another milestone. With federal funding support, GeoVax will sponsor a 10,000-participant, randomized, Phase 2b double-blinded study to compare the efficacy, safety and immunogenicity of GEO-CM04S1 with a U.S. Food and Drug Administration-approved mRNA COVID-19 vaccine. Preparations for the study are underway.
The federal awards supporting the study, totaling approximately $367 million, are funded by the Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response in the U.S. Department of Health and Human Services. A major portion of the award will be used by a contract research organization to recruit patients, oversee their vaccination and follow their outcomes.*
“As scientists who have developed various investigational vaccines over the years, we were extremely proud to learn about federal funding for such a large trial,” Dr. Diamond said. “We set out to design a COVID-19 vaccine that is safe and effective, superior to other vaccines, and we continue to believe it is due to its two-pronged approach against the virus.”
GEO-CM04S1 includes two antigens, one spike protein and one nucleocapsid protein, specific to the virus that causes COVID-19. The vaccine is built on a synthetic MVA platform (MVA, or modified vaccinia ankara, is an approved smallpox vaccine) designed by Felix Wussow, Ph.D., an assistant research professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.
After vaccination, the antigens delivered by the vaccine stimulate an immune response in the vaccinated person.
Trials for Immunocompromised Patients
Another unique feature of the vaccine is that it was developed with immunocompromised populations in mind.
City of Hope’s Alexey Danilov, M.D., Ph.D., the Marianne and Gerhard Pinkus Professor in Early Clinical Therapeutics and the Director of Early Phase Therapeutics Program at City of Hope, is leading a Phase 2 clinical trial that enrolls immunocompromised chronic lymphocytic leukemia patients to test how strong their immune responses are after receiving GEO-CM04S1 compared with the Pfizer-BioNTech COVID-19 vaccine.
“Patients who are immunocompromised have often shown a weak antibody response after FDA-approved COVID-19 vaccinations,” Dr. Danilov said. “GEO-CM04S1 might offer a better alternative for immunocompromised patients due to its dual-antigen approach and focus on boosting T cells.”
A trial that evaluates GEO-CM04S1 as a primary vaccine for blood cancer patients undergoing stem cell transplantation or chimeric antigen receptor (CAR) T cell therapy continues to enroll patients in multiple sites. Further Phase 2 clinical studies are planned.
Vaccine’s Promising Results So Far
For the Phase 1 study in healthy volunteers that took place at City of Hope and other institutions, Dr. Diamond’s team reported that people vaccinated with GEO-CM04S1 had a strong T cell immune response to both the spike and nucleocapsid antigens for six months after vaccination. Vaccinated people were equally protected against past COVID-19 variants of concern, such as Delta and Omicron.
Because GEO-CM04S1 focuses on a different arm of the immune system — T cells — it is capable of still imparting effective immunity despite variations in the virus that makes it resistant to many antibody therapies.
In contrast to the antibody-mediated immune response, T cell responses, also called cell-mediated immunity, last longer and may be an important source of long-term protection.
“In the continuing response to COVID-19, the U.S. government is seeking greater coverage and greater diversity in the components of COVID-19 vaccines,” Dr. Diamond said. “That may be why GEO-CM04S1 was selected as a promising next-generation COVID-19 vaccine. We hope that our vaccine will continue to move forward.”
History of Research and Development at City of Hope
Research and development of novel therapies and medications is a longstanding focus at City of Hope. Known for creating the technology used in the development of human synthetic insulin and numerous breakthrough cancer drugs, City of Hope’s unique research and development hybrid creates an infrastructure that combines the capabilities of an academic research center with a biotechnology company to enable researchers to pursue new treatments and technologies. In a span of one year, City of Hope submits more than 100 new drug applications to the U.S. Food and Drug Administration. The institution had 30 new drugs in development in 2022.
Dr. Diamond emphasized that many within City of Hope’s community helped make the vaccine’s development possible.
“It was really a team effort within City of Hope — from the patients and employees who volunteered for the clinical trial to leaders such as Dr. Harlan Levine of our health innovation team and Christoph Pittius and his technology licensing team, who worked on getting the vaccine licensed with an external company,” Dr. Diamond said. He added that The Carol Moss Foundation also provided $1.5 million to his team for clinical monitoring and development. “Our team could not do this on our own, and we are grateful for everyone’s support.”
*This project has been funded in whole or in part with federal funds from the Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under Other Transaction Number 75A50123D00005, and from BARDA, under contract 75A50120D00016/75A50123F33005.