On Jan. 10, 2020, Chinese scientists published the genome sequence of a novel virus by depositing a file in Genbank, a digital resource for DNA sequences at the NIH. People at the National Institute of Allergy and Infectious Disease used that sequence to make a vaccine, one of 11 now in Phase 3 clinical trials. From my inquiries at the NIH, the Moderna vaccine, as it is called, is the only one in a Phase 3 trial that is fully subscribed — 30,000 people have volunteered and have had both shots or will soon. Other vaccines — from Oxford and AstraZenica, from Pfizer, from Johnson and Johnson, and companies in Europe, China and Japan — may soon be at the same stage.
Let’s use the Moderna vaccine as an example, understanding that other vaccines will follow a similar course. (The Russians apparently have skipped Phase 3 and are vaccinating the general population. There are many vaccines and drugs that have passed phases 1 and 2, but have failed Phase 3 trials. Find a list on the FDA website.)
At this writing — Oct. 25, 2020 — we are waiting for medical centers that administered Moderna vaccine or placebo in Atlanta, Detroit or other hotspots of infection to report. This is an intense process: How sick is each patient? What is the viral load? Is the patient making antibodies from the vaccine? Have the data been checked and rechecked?
At this point, we come to one of the most exciting moments in experimental medicine. Let’s say that on Dec. 15, 2020, the people managing the database report 1,000 COVID-19 cases among the 30,000 volunteers. In a double-blind experiment, nobody knows who got placebo or true vaccine until the code is opened. In the best of worlds, all of the sick patients would have received placebo and all of the people who received vaccine would be healthy. If both groups had an equal burden of disease, the vaccine fails. If the people who got vaccine had half the cases of the people who got placebo, that is defined as success. A lot of answers can be teased out of a well-designed trial, including fraud in reporting.
Let’s imagine that by Dec. 30, the statistical analysis has been done and the vaccine has been deemed worthy — it protects almost all of the volunteers who received active vaccine either completely or by restricting their disease to mild cases.
At this point, the trial does not stop; the placebo-treated patients will be offered real vaccine, as happened in 2014 with Ebola. All patients, in the case of the Moderna vaccine, will be followed for two years to learn how long antibody and T cell responses last (a friend is in that trial).
There are faster ways to test vaccines — by infecting healthy young volunteers to determine whether those who get a vaccine are protected. A trial of this nature does not strike me as a good idea because it may not yield meaningful results and is not worth the risk.
Imagine now that it is late January and there is enough FDA-approved vaccine to distribute. Some vaccines need to be frozen on dry ice, and FedEx, UPS and other companies are prepared for frozen packages. Scientists and clinical labs know how to work with cold temperatures — many of their supplies arrive on dry ice or even in liquid nitrogen. Eventually the Oxford/AstraZenica vaccine will be available and it requires only refrigeration. Distribution will be through established channels, which are being reinforced. I do not believe the military will be heavily used, except for distribution to the armed forces and in difficult places.
When will the general public get vaccinated? First in line are health care providers, who may number between 17 and 20 million. There are 80 million essential workers and a lot of vulnerable people in nursing homes. We have a fluid situation but widespread vaccination should be available, perhaps in June as CDC has been saying for some time. People may refuse to take a shot, but I am planning to take the first one available.
In 1947, a smallpox outbreak hit New York City. Within a week, millions of people were vaccinated and we can do that again. It was not easy but that effort is a seminal moment in the history of public health. In the end, we face more than a question of vaccination; it is a test our abilities. Resiliency is a test of nations.
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Richard Kessin, Ph.D., is professor emeritus of pathology and cell biology at the Columbia University Irving Medical Center. Reach him at Richard.kessin@gmail.com. He will offer a coronavirus course at the Taconic Learning Center in January.
