Publication in Nature Communications demonstrates robust neutralizing antibodies and T cell responses against SARS-CoV-2
Phase 1 clinical trial currently enrolling participants
A City of Hope investigational vaccine produced strong protective immunity against SARS-CoV-2, including neutralizing antibodies that recognize the current dominant circulating form, which is a mutant of the original Wuhan strain, according to research published today in Nature Communications. The vaccine is now being tested in a phase 1 clinical trial at City of Hope, an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases.
The investigational vaccine generated abundant neutralizing antibodies, which prevented the virus from infecting healthy cells, and produced strong responses by T cells against the virus’ spike (S) and nucleocapsid (N) antigens. The strong T cell response could provide long-term protection that may protect recipients of the vaccine against future SARS-CoV-2 outbreaks.
"Our investigational vaccine aims to address one of the challenges in combatting coronavirus infections — immunity against these viruses can be short-lived, less than six months in some COVID-19 patients," said Don J. Diamond, Ph.D., a professor with City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation who specializes in vaccine research. "City of Hope wanted to improve on the vaccine’s capability of stimulating protective immunity. We did that by activating T cells, which constitute the other powerful arm of the immune system.
"We spurred the production of CD4 and CD8 T cells of various types, including memory T cells," Diamond said. "These T cells can live in the blood for a longer time than antibodies and attack a pathogen should it appear at a later time."
Diamond and his team also studied whether the mice that received the vaccine would still have immunity if SARS-CoV-2 mutated. To do that, they inserted various genetic sequences from SARS-CoV-2 into test viruses called pseudoviruses. The team found that antibodies, generated by the mice in response to the vaccine, prevented infection of susceptible cells by the pseudoviruses.
"Despite the fact that our investigational vaccine had a slightly different genetic sequence, it’s capable of preventing a slightly mutated version of SARS-CoV-2, which is now the dominant circulating strain in the U.S., from getting into a cell," Diamond added.
To produce the investigational vaccine, a team of City of Hope scientists, led by Felix Wussow, Ph.D., and Flavia Chiuppesi, Ph.D., both City of Hope assistant research professors in the Department of Hematology & Hematopoietic Cell Transplantation, together with Diamond, first developed a unique synthetic modified vaccinia ankara (sMVA) platform technology to house the genetic components that make up the vaccine candidate at a molecular level. MVA is a safely modified poxvirus that is approved by the Food and Drug Administration for the prevention of smallpox and monkeypox, and is also included in the federal government’s Strategic National Stockpile for lifesaving use during a public health emergency.
"The clinical and research benefit of this platform is that it can be adapted for any infectious disease and it can be done very rapidly," Diamond added.
For the COVID-19 investigational vaccine, the platform was used to rapidly produce the synthetic virus, which then started to replicate its DNA within a cell. The virus produced large quantities of the SARS-CoV-2 S protein, which led to the production of neutralizing antibodies against the virus, and the N antigen. Both the S and N antigens also elicited a strong T cell response for the mice to mount an immune response against the virus. All mice who received the vaccine produced these results with no side effects.
The MVA platform has similarities to the Triplex vaccine developed by City of Hope against cytomegalovirus, a herpesvirus that can cause complications for stem cell transplant recipients. Research published in Annals of Internal Medicine showed that patients in the phase 2 randomized multicenter trial who received Triplex were less likely to develop health complications related to the herpesvirus than patients who did not take it. The p53MVA vaccine, also developed at City of Hope, is continuing to be used in combination with cancer drugs, such as pembrolizumab and gemcitabine, against solid tumors.
Previous experience with MVA-based vaccines has shown few side effects due to the highly attenuated virus-based vaccine makeup.
"City of Hope has extensive experience developing and using MVA vaccines, which have a record of safety and efficacy," Diamond noted. "We chose this vaccine platform because MVA vaccines have been shown to be safe and effective in immunocompromised patients, such as cancer and transplant patients, and can produce an immune response in less than 14 days with long-lasting T cell immunity of at least one year.
"Because City of Hope has expertise in testing these vaccines, we expect that the investigational COVID-19 vaccine will also produce superior T cell responses in people and will be safe for volunteers to take under our close monitoring," Diamond said.
City of Hope aims to complete its phase 1 clinical trial by the end of March 2021.
About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nation’s "Best Hospitals" in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
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