The genome sequence of the SARS-CoV-2 virus was deposited on a National Institutes of Health server in early January 2020. Within days, scientists all over the world started to use the sequence to make vaccines.
More than 135 vaccines are at earlier stages of development. Three vaccines are now approved for limited use; eight vaccines are in large-scale Phase 3 clinical trials; 13 are in expanded Phase 2 safety trials; 21 are moving through Phase 1 safety testing. These numbers are being curated by the New York Times and the World Health Organization and are updated frequently. Search for the NYT Coronavirus Vaccine Tracker; the Times is not failing and will keep you updated about this and other aspects of the pandemic.
How the vaccines work
All of the vaccines are designed to present a SARS-CoV-2 spike protein to the human immune system and provoke the production of circulating antibodies and T cells that kill lung or other cells infected with the virus. After a vaccination or illness, the immune response subsides, but many antibody-producing B cells and cell-killing T cells are banked. When infection occurs, thousands or millions of lymphocytes leap into action and block or minimize the infection. Fortune favors a prepared immune system.
With some vaccines, the banked cells last a long time; with others, only a few months. The spike protein is a string of about 400 amino acids, but for each position in the string, there is a choice of 20 possible amino acids. During its synthesis, the protein folds into a spike shape and is assembled into the SARS-CoV-2 virus particle. During infection, the tip of the spike protein grasps a protruding protein on the surface of human cells and the attached virus is pulled inside, where it unfolds and starts the production of much more virus.
The vaccines in Phase 3 testing are all products of genetic manipulation, unlike the vaccines of Salk, Sabin, Jenner or Pasteur, which used viruses or bacteria that were attenuated and did not cause disease, but little else was known about them. The newer molecular technology is more precise and gives vaccine makers the advantage of speed.
In one approach, scientists insert the gene that carries the information to make a viral protein into another virus that causes mild disease and has been further weakened. Collaboration between the Jenner Research Institute at Oxford and AstraZeneca, a large British-Swedish drug manufacturer, both excellent organizations, is instructive. Universities and research institutes are good at basic research and creating the initial recombinant virus, but not very experienced in large-scale production, which AstraZeneca is.
The collaboration used a weakened chimpanzee adenovirus that normally causes colds, with an inserted COVID-19 virus spike protein gene. It is now entering Phase 3 trials with 30,000 volunteers. The vaccine is called AZD1223 and its assigned number at Clinicaltrials.gov is NCT04316746. Type that number and AZD1223 into Google and you will find the study and how to join it. Preliminary results are expected in December 2020.
A vaccine method that is intriguing to me is purely chemical. Recipients get no live or dead virus, which can be reassuring for some people. The new method makes the mRNA the intermediate that provides instructions for the synthesis of the spike protein, but all in a test tube. The scientists wrap the coding mRNA in lipid and inject it into macaques or humans, where it enters cells and uses their protein synthesis capacity to make spike protein.
In macaques, the mRNA-1273 vaccine successfully defends the host from the coronavirus. This novel vaccine is the product of Tony Fauci’s National Institute of Arthritis and Infectious Disease and a company called Moderna that specializes in RNA-based defenses against infectious disease. This vaccine is also in Phase 3 trials on 30,000 people. To find the list of all clinical trials, visit www.ClinicalTrials.gov. (As of Sept. 1, there were 1,397 clinical trials involving COVID-19). You will also find medical centers involved in the trials at that website (enter code identifier NCT04470427). Being a participant requires commitment because the people running a trial want to know if you produce antibody and new T cells in response to a vaccination and how long the response lasts, which means occasional blood tests. They want to know about side effects. They are required to have participants of all ages and ethnicities.
The new techniques for vaccine production are effective and fast, but we have to know about dangerous viruses before they break into the human population. New technology will not do us much good if we ignore pandemic preparedness plans, eliminate virus surveillance programs, leave the World Health Organization, ignore the advice of the CDC, and denigrate the scientists and physicians who are trying to keep us alive.
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Richard Kessin, Ph.D., is professor emeritus of pathology and cell biology at Columbia University’s Irving Medical Center. He can be reached at Richard.kessin@gmail.com.
