The unique dual-antigen design of a COVID-19 investigational vaccine developed by City of Hope scientists, now licensed to GeoVax Labs Inc., confers long-lasting immunity that is effective against variants of concern such as Omicron, according to a study published in iScience.
The vaccine, known as COH04S1, includes two antigens, one spike protein and one nucleocapsid protein, specific to the virus that causes COVID-19. After vaccination, the antigens delivered by COH04S1 stimulate an immune response in the vaccinated person.
In the study, City of Hope researchers led by Don J. Diamond, Ph.D., professor in City of Hope’s Department of Hematology & Hematopoietic Transplantation, reported that people vaccinated with COH04S1 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 variants of concern, such as Delta and Omicron. This is the first time the investigators have looked at the nucleocapsid-specific T cell immune response six months after vaccination and across the different variants.
Lasting T Cell Response
“Our findings are very relevant because we show that one type of immune response, the neutralizing antibody immune response, declines over time in vaccinated people and is reduced in response to variants. But we don’t see this with the T cell immune response,” said Flavia Chiuppesi, Ph.D., an assistant research professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation and the study’s lead author. “The T cell response stays stable over time [and at least up to 6 months] and also across variants.”
The virus that causes COVID-19, SARS-CoV-2, continues to evolve, resulting in different forms of the virus called variants. Because the City of Hope vaccine focuses on a different arm of the immune system, 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.
“The neutralizing antibody response declines over time and recognizes less and less of the variants encountered,” said Chiuppesi. “But your T cell response remains strong, and this acts as a second line of defense.”
In the study, investigators studied the antibody-mediated and T cell-mediated immune responses of people vaccinated with COH04S1 as part of a clinical trial and the immune responses of health care workers vaccinated with the Pfizer BNT162b2 vaccine.
The investigators found that people vaccinated with COH04S1 had a robust antibody response to the spike and nucleocapsid antigens in the ancestral SARS-CoV-2 virus (that is, the virus before it began to evolve), whereas people vaccinated with BNT162b2 had a robust response to the spike antigen only, consistent with the single-antigen design of that vaccine. In both groups, however, neutralizing antibody responses at six months against variants of concern such as Delta and Omicron were low or undetectable.
Cell-mediated immunity, by contrast, remained strong in both groups, even against Omicron. At six months after vaccination, both groups had strong spike-specific immune responses to SARS-CoV-2 and its variants, including Omicron. But the group vaccinated with COH04S1 also had strong nucleocapsid-specific immune responses.
Added Antigen Beneficial
These findings extend previous findings from other COVID-19 vaccines showing that T cell responses to the spike protein are maintained and further show that T cell responses to nucleocapsid are sustained for six months after vaccination. The study’s findings support the incorporation of both spike and nucleocapsid antigens into COVID-19 vaccines as a critical second line of defense against the emerging variants of concern.
“In the continuing response to the pandemic, the U.S. government is proposing that greater coverage and greater diversity in the components of COVID-19 vaccines be an objective in the future,” said Diamond. “Our vaccine meets this goal.”
The City of Hope 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. The MVA platform is widely used to develop new vaccines for infectious diseases and cancer. The safety and effectiveness of COH04S1 is currently being studied in a Phase 2 clinical trial of immunocompromised cancer patients and a Phase 2 trial investigating COH04S1 as a booster in healthy volunteers.