19 Jan. 2021. A vaccine protecting against multiple Covid-19 viral variations is in development, with an early-stage clinical trial expected to begin soon. Gritstone Oncology Inc. in Emeryville, California designed and is testing the vaccine with support from the Bill and Melinda Gates Foundation and National Institute of Allergy and Infectious Diseases, or NIAID, but financial details were not disclosed.
Gritstone Oncology develops treatments for cancer and infectious diseases based on the specific DNA composition of target cells called neo-antigens. The company first created its technology, called Edge, for cancer to evaluate DNA from each patient’s tumor using genomic sequencing and bioinformatics to identify individual tumor-specific neo-antigens. Gritstone then applies its own algorithms with artificial intelligence to identify the most likely neo-antigens to activate an immune response, and delivers personalized synthetic neo-antigens for the patient as a vaccine, either on their own or with other therapies. Among Gritstone’s own treatments are T-cell receptors, naturally occurring proteins modified to target other characteristic proteins on the surface of target virus or cancer cells.
For a Covid-19 vaccine, Gritstone Oncology applies its Edge technology to targets on the SARS-CoV-2 virus responsible for Covid-19 infections. The company licensed from La Jolla Institute for Immunology validated epitopes, binding sites for antibodies and T-cells on antigen proteins recognized by the immune system, for SARS-CoV-2 viruses. La Jolla Institute derived the epitopes from analyzing hundreds of recovering Covid-19 patient blood samples.
Targeting the spike protein and more virus sites
Gritstone Oncology says its so far unnamed vaccine targets epitopes on the spike protein, like other vaccines, but also on other areas of the virus for attack by T-cells. The company says its vaccine is coded in messenger RNA and uses adenovirus vectors for delivery. The Gates Foundation supported preclinical development of the vaccine, while NIAID is partnering with the company on an early-stage clinical trial.
Preclinical tests, says the company’s chief scientist Karin Jooss, show the vaccine can produce multiple immune responses against more regions of the SARS-CoV-2 virus. “Our preclinical work,” says Jooss in a company statement, “has shown that our SARS-CoV-2 vaccines can induce sustained, high-titer neutralizing antibodies and CD8+ T cell responses against the spike protein, plus a broad CD8+ T cell response against epitopes from multiple viral genes outside of spike.”
Gritstone says the early-stage clinical trial will be conducted through Infectious Diseases Clinical Research Consortium, a network of medical centers established by NIAID to host clinical studies of vaccines, but other aspects of the trial are still being prepared.
Infectious disease specialist Daniel Hoft at St. Louis University in Missouri, and principal investigator of the study, says this and other new vaccines can serve a vital role in protecting the public health as the SARS-CoV-2 virus mutates over time. “It is important that we move forward with developing these next generation vaccines,” notes Hoft, “because we do not yet know whether the existing vaccines that have been granted emergency use authorization will provide long-term immunity or prevent transmission. Improved vaccines that can accomplish these additional benefits may be needed to continue mitigating the ongoing pandemic.”
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