COVID-19 continues to impact our communities, our country and nations across the globe. Currently, several vaccines are in development with the hopes of preventing future spread of this virus. As we field growing interest and curiosity on this topic, now is a good time to talk with UVM Medical Center Infectious Disease Specialists Kristin Pierce, MD, and Beth Kirkpatrick, MD, director of the Vaccine Testing Center. The Vaccine Testing Center at UVM has extensive experience with vaccine clinical trials and has been involved with vaccine studies for the last 20 years, as part of the UVM Larner College of Medicine and UVM Medical Center. The team has studied vaccines for Dengue, Cholera, Camplyobacter, Cholera, Typhoid, Anthrax, West Nile Virus, and Zika.  

How do vaccines work to prevent illness?

The general idea of a vaccine is that to protect a person from an infection they are exposed to a safe amount of that infectious agent (here a virus), either in a weakened version or with a small part of the infectious agent. The body then naturally makes its own immune response that then protects the person from illness when they are exposed to the real disease in the future. There are many kinds of vaccines but all follow this principle.

Why are there so many vaccines in development for COVID-19?

There are approximately 135 vaccines in different stages of development worldwide and around 10 in advanced testing. There are so many for two reasons. The first and easiest is that one company cannot make enough for everyone who needs or wants a vaccine to receive one. Given that there are over seven billion people on the planet – that is a lot of doses. Also, not everyone will be able to receive the same type of vaccine. The development of several vaccines would allow the vaccine to be safe and effective in people of all ages, demographics and underlying medical conditions. For example, some vaccines, such as the vaccine for chickenpox, cannot be given to people with certain types of medical conditions (pregnant women or people whose immune system does not function well due to underlying medical problems). So we need several types of vaccines to make sure we have one for everyone who needs one.

What are the phases of a clinical trial?

All new vaccines go through a series of stages from conception to development to licensure. This is regulated tightly by the U.S. Food and Drug Administration (FDA). First, is the pre-clinical phase. This is the research that is done before it is ever given to people. It ensures that the vaccine researchers understand everything they can about the pathogen or infectious agent (bacteria, virus) and how it makes people ill. This stage involves studying the bacteria or virus in the laboratory, to understand how to develop a vaccine against it.

Once the vaccine has been designed, it is tested often in animals to see if it is safe and to see if it generates an immune response (stimulates the body to fight the infection). Then, after a long process of data review and approval by FDA, vaccines move into people in “clinical trials.” The vaccine has to succeed in its safety measures in each phase before proceeding to the next.

Phase 1 involves giving the vaccine to a very small number of people who volunteer to participate. This allows the researchers to ensure that what was proven to be safe in the animal models is safe and doesn’t cause reactions in healthy human volunteers.

Phase 2 involves giving it to a larger number of healthy human volunteers – for more safety information but also to see how well it produces an immune response and to figure out dosing (how much, how often). 

Phase 3 involves larger numbers of volunteers and is really focused on whether it actually works! That is to say, does the vaccine prevent disease? These are often very large (tens of thousands of volunteers). After this the FDA may allow licensure of the vaccine for general use

Phase 4 (post-licensure) studies track recipients to keep compiling data on very rare side effects.

What does participation in a vaccine trial look like?

Each clinical trial is different. However, two things important for all clinical trials is that first, all clinical trials are voluntary. Secondly, each participant goes through what is called “Informed Consent.” This means that no one can participate in a clinical trial without giving their consent or agreement to do so. In this process, the volunteers, in partnership with a member of the study team, encourages and ensures that each individual learns about the trial, the risks and benefits, before deciding whether or not participation is right for them. For the COVID-19 vaccine trials progressing nationally, these studies are all aligned to be similar. Most involve a series of two vaccines one month apart (some have one vaccine) with up to eight study visits and two phone calls over a two year period. In-person study visits include working with a study clinician, nurse and assistants; review of whether the volunteers meet eligibility for the study, a review of their current medical problems, a short exam, blood draw and vaccination. After the vaccination visits, follow up visits are shorter. There are also check-ins by phone or computer.

How do you determine if a vaccine is successful?

There are a lot of ways to answer this. Specific to COVID-19 vaccines, the test of success is part of the study design. These vaccine studies will demonstrate if the vaccine decreases the clinical illness of COVID-19 when compared to those without a vaccine. In general, vaccines are successful when they are effective at preventing disease in an individual and in a population (a large numbers of people). However, it is important to think about vaccines as a tool in a toolbox against the spread of COVID-19 infection. Masking, physical distancing and handwashing are all still important public health measures that will help prevent the spread of COVID-19 until an effective vaccines (or other measures) can be developed and administered to the global population.

How is the process moving so quickly?

It’s true that normally this process can take years, sometimes decades, from start to finish to develop a vaccine. One reason that pace for a COVID-19 vaccine has taken off so quickly is that there is funding for vaccine development on a global scale. The entire world is looking for an effective vaccine; these are unprecedented times and everyone is rolling up their sleeves. Several of the vaccines farthest along in clinical testing are those that that have a vaccine backbone (or platform) previously developed against other viruses (Ebola) as well other Coronaviruses like Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS). In this way a lot of the early work – especially the preclinical work – has already been done, and many of these similar vaccines have been well studied in human volunteers. In addition, these vaccines are being given top priority over almost all other products in the pipeline; this saves a lot of time.

How long will immunity last?

This is one of the very important questions these vaccine trials are working to answer, but as of now, is still unknown. The ideal situation would be that you only need to be vaccinated once, which is true for some vaccines. However, it may require a “booster dose” every few years, or it could be that we need to get the vaccine on an annual basis like the flu vaccine.

Why are studies looking for people at high risk?

The priority for COVID-19 vaccines is to protect person at highest risk of severe disease and exposure, so we must study this same group of people to know it works for them.

Could someone catch COVID-19 from the vaccine?

No. The vaccine is made from only a piece of protein from the virus. For any virus to replicate (grow) and cause disease it needs to be able to infect our cells and to grow inside those cells. This would not be possible from this type of vaccine technology.

Will participants be exposed to COVID-19?

No, they will not be intentionally exposed to COVID-19. Following vaccination, individuals will be followed over two years to see if the vaccine prevents COVID-19 infection as volunteers move about their everyday lives.

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