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Ellis: Understanding the ‘vaccine stage’ of this pandemic

By Glenn Ellis

There are more vaccines in the pipeline now for COVID-19 than ever for any infectious disease.

At some point the number of vaccines available from different pharmaceutical companies is going to create public confusion, creating yet another challenge in the plans to distribute the COIVD vaccines and put them in arms. According to the New York Times, researchers are currently testing 68 vaccines in clinical trials on humans, and 20 have reached the final stages of testing.

At least 90 preclinical vaccines are under active investigation in animals. All of them are trying to achieve the same thing – immunity to the virus, and some might also be able to stop transmission.

There are four categories of vaccines in clinical trials: whole virus, protein subunit, viral vector and RNA or DNA. Some of them try to smuggle the antigen into the body, others use the body’s own cells to make the viral antigen.

Most of us are most familiar with the messenger RNA vaccine from Pfizer and Moderna pharmaceutical companies. But how much do you really understand about what they are, and how they work?

Many conventional vaccines use whole viruses to trigger an immune response. There are two main approaches. Live “thinned down” vaccines use a weakened form of the virus that can still duplicate without causing you to get sick. Inactivated vaccines use viruses whose genetic material has been destroyed so they cannot replicate but can still trigger an immune response. Live vaccines may risk causing disease in people with compromised immune systems.

Subunit vaccines use pieces of the virus to trigger an immune response. Doing so reduces the risk of side effects, but it also means the immune response may be weaker. This is why they often require a “booster shot” to help the immune response. An example of an existing subunit vaccine is the hepatitis B vaccine. Completing the hepatitis B vaccine series of shots (2, 3, or 4 doses, depending on the manufacturer) is needed to be fully protected.

Viral vector vaccines also work by giving cells genetic instructions to produce antibodies. But they differ from RNA or DNA vaccines in that they use a harmless virus, different from the one the vaccine is targeting (COVID-19), to deliver these instructions into the cell. Vaccines using this method include one for adenovirus, the virus responsible for the common cold. As with RNA vaccines, our own cellular machinery is hijacked to produce antibodies from those instructions, in order to trigger an immune response. However, since there is a chance that many people may have already been exposed to the viruses being used as vectors, some may be immune to it, making the vaccine less effective.

Both RNA and DNA use genetic material to provide cells with the “instructions” to make the foreign substances which creates an immune response in the body, especially the production of antibodies, to attack the viral spike protein in COVID-19. Once this genetic material gets injected into our arm, it uses our cells’ protein factories to make the antigens. A downside, however, is that so far, no DNA or RNA vaccines have ever been used in humans. In addition, RNA vaccines need to be kept at ultra-cold temperatures, which is proving challenging for communities that don’t have specialized cold storage equipment.

There are a couple other considerations that may be helpful to understand and pay attention to as we move through the “vaccine stage” of this pandemic. The two different mRNA vaccines available now showed remarkable effectiveness of about 95 percent in preventing COVID-19 disease in adults during the clinical trials. Because of scarce vaccine, the United Kingdom has stretched the interval between doses. I have been following the discussions and news reports about reducing the number of doses, extending the length of time between doses, changing the dose (half-dose), or mixing and matching vaccines in order to immunize more people against COVID-19. These are all reasonable questions to consider and evaluate in clinical trials.

However, at this time, now that the vaccines have been made available for the general population, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining vaccine’s potential to protect the population from COVID-19. Some virologists worry that extending the dosing interval might result in millions of people with only partial immunity as they wait for their second dose—a potential breeding ground for vaccine-resistant mutations.

The emerging mutations of the coronavirus have been in the news ever since that first mutation caught scientists’ attention in England in December. Now we are finding that not only is it more transmissible than previously circulating versions of the COIVD-19 virus, but now, they’re also focusing on a potential new threat: mutations that could do an end run around the human immune response. Such “immune escapees” could mean more people who have had COVID-19 remain susceptible to reinfection, and that proven vaccines may, at some point, need an update.

“Stay informed; stay vigilant; stay safe…Information is the Best Medicine”.


Glenn Ellis, MPH is a Visiting Scholar at The National Bioethics Center at Tuskegee University and a Harvard Medical School Bioethics Fellow. He is author of Which Doctor? and Information is the Best Medicine. For more good health information visit: www.glennellis.com.