Can we trust the new Covid-19 vaccines? Some context.

By Peter Katona and Seth Freeman

Vaccines protect against disease by performing a kind of genetic judo on the body’s immune system. The precise mechanisms vary widely, but in each case an outside agent is introduced into the body which stimulates the production of antibodies to defend against the targeted pathogen. The agent might also arouse the body’s white cells to attack the invader.

The first known vaccine was used against smallpox centuries ago in China, perhaps as early as the 11th Century, by an enigmatic healer, whose name has been lost to history. The healer would have had no scientific understanding of disease, but he was a sufficiently cunning observer of the natural world to note that people who contracted smallpox (variola), which killed thirty percent of those infected, subsequently had an immunity to the disease. The healer would cut the skin of a healthy person and introduce pus from a sick patient into the wound, a process later known as variolation.

In Europe during the Middle Ages nearly everyone contracted smallpox. The survivors became immune, but would have obvious, recognizable facial scars. As a result, a smooth face, unmarked by pox, could keep someone from getting a job; employers were reluctant to hire a person with a 30% likelihood of dying in the near future.

In the early 18th Century travelers brought the practice of variolation from the Far East to Turkey. Lady Mary Wortley Montagu, wife of the English ambassador to the “Sublime Porte,” learned of the technique and advocated for its use in the British Isles, from where it spread more widely. Catherine the Great of Russia was famously variolated in 1768, and escaped smallpox. She called those in her day who violently opposed the treatment “blockheads.” During the Revolutionary War many men were reluctant to join Washington’s army out of fear of dying from smallpox even more than of dying in battle. Washington mandated variolation for all non-immune troops, a decision considered pivotal in his ultimate victory.

The big breakthrough in developing safer vaccines came about twenty years later and is ascribed to English physician Edward Jenner. For many years he had heard the local talk that dairy maids never got smallpox although they were frequently infected with the similar, although less serious disease, cowpox. While practicing medicine in Gloucestershire Jenner located a dairymaid with fresh cowpox sores and used the pustules to inoculate a healthy young boy. The boy developed some fever and pain and suffered other mild symptoms of the pox, but ten days after the inoculation he was much improved. Two months later Jenner inoculated the same boy with active smallpox. The child did not develop the disease. Jenner later repeated the experiment and was able to conclude — and convince the world — that the cowpox inoculation had conferred immunity.

Most importantly, Jenner confirmed the insight that a weakened version of a similar pathogen can have the effect, as we understand it now, of stimulating the immune system to produce antibodies without giving the patient the target disease. His treatments were called “vaccines” from the Latin word, vacca, for cow. In the twentieth century, building on this core concept, scientists developed antiviral vaccines using a variety of more refined strategies: live attenuated virus, dead virus, parts of another benign virus such as adenovirus, and molecules that resembled the virus.

Now, in 2020 and into this year, scientists have developed vaccines against the Covid-19 virus using an even more creative, and quite possibly safer, technology — modifying genetic material of the virus itself by taking a portion of its unique genetic code, in the form of messenger RNA (mRNA), to induce the body’s immune system to produce antibodies aimed against the specific protein spikes, the stringy knobs which we have all seen in the images of cells of Covid-19. These proteins are the weapons the virus uses to breach the cell walls and to invade healthy cells. By instructing the body to create antibodies to neutralize the protein spikes, the new generation of vaccines, at a very high rate of efficacy, render the coronavirus harmless in the body.

The science behind the use of mRNA in a vaccine is not something researchers cooked up overnight in response to the coronavirus. It has been around for decades. Hungarian researcher Katalin Karikó first proposed using mRNA to fight infectious disease and cancer in the 1990s. In 2005 Karikó, her collaborator Drew Weissman, and others advanced the technology significantly, solving a major barrier to the use of mRNA in the body — the tendency of the immune system to detect and attack the synthetic RNA as it would any invader — through the use of very cold temperatures. Five years later, in 2010, scientists recognized the potential for creating vaccines which could leverage the methods developed by Karikó and Weissman to slip inside the body and reprogram the immune system to fight specific pathogens.

It was extremely helpful, therefore, when very early in the Covid-19 outbreak, Chinese researchers sequenced the entire genome of the virus and released their findings to the world. With this data scientists at BioNTech and Moderna and elsewhere had a ready roadmap enabling them to quickly create the bits of genetic “computer” code at the core of the new vaccines, ushering in an exciting new age combining biotech and information tech. An unprecedented level of worldwide cooperation in the scientific community, the cutting of vaccine approval wait times — without cutting any corners in the evaluation process — and the high incidence of Covid cases, which helped get trial results sooner, all combined to produce what increasingly appear to be extremely safe, highly effective vaccines in record time.

Clinicians and scientists understand this careful, decades-long, logical, sequential process of development as well as the ingenious novel mechanism by which the new mRNA vaccines act on the human immune system. They are also heartened by the superb efficacy and safety of the new vaccines as demonstrated in test trials. It is for all these reasons that they are so positive and upbeat about these treatments — and so anxious to use them to treat their patients, their families and themselves.

We are still in the fight against Covid-19 and its emerging mutant strains. The game is close, but we are in the fourth quarter. The best shot we can take is the one in the arm.

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Peter Katona, MD, is Clinical Professor of Medicine at the UCLA David Geffen School of Medicine and Adjunct Professor of Public Health at the UCLA Fielding School of Public Health. He chairs the UCLA Covid-19 Infection Control Working Group.

Seth Freeman, MPH, is an Emmy-winning writer/producer for television, a playwright and a journalist, who writes about technology, policy and public health.

Seth Freeman, MPH, is a journalist, a playwright, and an Emmy-winning writer/producer of television, who created the series Lincoln Heights.

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