Dr. Donald Forthal

The first vaccine was developed in 1796 by British physician and scientist Edward Jenner, after he had intuited that dairy workers’ resistance to smallpox resulted from their exposure to the much milder cowpox. (Jenner derived his term “vaccine” from vacca, the Latin word for cow.)

It took scientists nearly another century to begin to understand that vaccines work in the human body by stimulating the formation of antibodies. It wasn’t until the 1970s that a worldwide effort led to the effective eradication of smallpox, which had plagued humankind for more than 3,000 years.

While vaccines have made remarkable strides in recent decades, nothing compares with the accelerated development and testing of the two COVID-19 vaccines given emergency approval by the U.S. Food and Drug Administration late last year. On Dec. 16, 2020, just over a year after the global pandemic had quietly started in Wuhan, China, UCI Health received 3,000 doses of the Pfizer-BioNTech vaccine and began administering them to its healthcare workers, according to Centers for Disease Control and Prevention guidelines. The following week, 2,800 vials of the Moderna vaccine were also made available. Both vaccines require a second dose three or four weeks after the first. The goal is to ultimately inoculate some 15,000 UCI Health employees.

“The priority is based on healthcare workers’ level and length of exposure to high-risk patients,” explains Dr. Donald Forthal, chief of the UCI School of Medicine’s Division of Infectious Diseases. (He has received both doses.)

Forthal earned an M.D. at UCI in 1979 and worked at the CDC, the World Health Organization and elsewhere before returning to UCI in 1989 to teach and conduct research. Along with heading the infectious diseases division, he is a professor of medicine in UCI’s School of Medicine. He has a joint appointment in the Department of Molecular Biology & Biochemistry and is a member of both the Center for Virus Research and the Institute for Immunology. UCI Magazine contributing writer Jim Washburn spoke with Forthal in January about the science behind the vaccines – and their prospects.

What can you tell us about these new vaccines and how they perform in the body?

Both the Pfizer and Moderna vaccines are not typical compared with those that have been licensed in the past. In fact, these are the first mRNA [messenger ribonucleic acid] vaccines to be approved, in this case via an EUA [emergency use authorization by the FDA]. Previous mRNA vaccines have been used in studies, but they’ve never before been licensed.

Every time our bodies see foreign proteins – whether in the form of a bacteria, virus, parasite or something else – we are built so that we can make antibody responses against those proteins. Humans can generate a vast repertoire of antibodies that can bind to just about any protein that isn’t a normal human protein.

The Pfizer and Moderna vaccines are using mRNA that encodes the SARS-CoV-2 spike protein, which is the target for neutralizing antibodies – that is, antibodies that will block the virus from infecting cells of the human host.

What happens is you inject the mRNA, it gets taken up by cells, and in those cells, the spike protein of SARSCoV-2 is made. That protein is recognized by B cells, which will produce antibodies that can recognize and inhibit the real virus if it appears in the body.

What would you tell a person who is hesitant to get a coronavirus vaccine?

What we know so far about the Moderna and Pfizer vaccines is that they have undergone testing now in a fairly large group of people who were followed for at least two months, per the FDA’s guidelines for safety data. That’s rather reassuring, because most severe side effects will probably occur within six weeks of a vaccination.

I think people can be confident that there aren’t going to be any severe, unexpected problems. There are side effects to every vaccine, and sometimes it takes millions of injections, not tens of thousands, to discern the full spectrum. But as it looks now, serious side effects are not going to be at all common.

The anti-vaxxers, I think, do pose a real problem. The WHO has identified vaccine hesitancy as one of the top 10 threats to global health. It’s something we just have to deal with, through educating people and pointing out the benefits versus the risks. To address one myth: There is no danger of incorporation of the vaccines’ mRNA into the genes of a vaccinated individual, primarily because the mRNA is degraded and is not converted into DNA. In other words, it does not change an individual’s DNA.

“There is no danger of incorporation of the vaccines’ mRNA into the genes of a vaccinated individual, primarily because the mRNA is degraded and is not converted into DNA. In other words, it does not change an individual’s DNA.”

What will we see in 2021? Will life get at all back to normal?

This is a very infectious virus and it appears to have become more infectious over time. Because people often don’t display symptoms or don’t get very sick, they don’t isolate themselves, and that has allowed the virus to explode into human society. When we saw the rapid spread of the infection in Wuhan and then throughout Asia, it seemed inevitable that it would spread here, given all the travel between Asia and the U.S. At UCI, we started preparing for it because we could see the potential for medical facilities to be overwhelmed.

There’s no question about the virus’s ability to sustain itself and spread, but in respect to vaccine development, the virus has proved to not be all that formidable. Within months of the initial reports of this infection, several vaccines had been developed, and there will be more. Some of them, like the AstraZeneca vaccine, have had setbacks and may not be as effective as the two that currently have approval. But the bar seems to be set pretty low for generating the kind of immune response needed to prevent SARS-CoV-2, so I think there will be additional effective vaccines. The virus is nowhere near as formidable, for example, as HIV, where after decades we still are not real close to getting a vaccine.

With SARS-CoV-2, I can only depend on what people at the CDC and the National Institutes of Health are saying, but they’re looking at a much wider distribution of the vaccines by spring. I’m hopeful that there will be substantial decreases in the number of cases by then, but the rollout has been slow, and lots of people are still not masking or keeping their distance. So spring may be optimistic with respect to getting back to normal. It really depends on how quickly the vaccines can be distributed, how many people agree to get them and, ultimately, how effective and durable the immune response to the vaccine is. There remains some question of exactly when we’ll turn the corner on this, but I don’t doubt that we will.