COVID-19 Vaccine Update: What You Need to Know
An infectious disease specialist explains how COVID-19 vaccine candidates work and their role in fighting the pandemic.
Scientists from throughout the U.S. and around the world are racing to develop vaccines to help turn the tide of the COVID-19 pandemic. NewYork-Presbyterian is testing two vaccines that take aim at SARS-CoV-2, the virus that causes COVID-19. And in recent weeks, there’s been encouraging news. Preliminary data from vaccines manufactured by Pfizer and Moderna showed them both to be 95% effective. Data from late-stage clinical trials of AstraZeneca’s vaccine was also promising: it was on average 70% effective.
Dr. Magdalena Sobieszczyk, chief of the Division of Infectious Diseases at NewYork-Presbyterian/Columbia University Irving Medical Center and professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, provides an update and answers questions about the COVID-19 vaccine candidates and the future of the pandemic.
How many vaccines are in the pipeline and how many are being tested in people?
Right now, more than 100 COVID-19 vaccine candidates are in different stages of development. Of those, over 40 are being clinically evaluated, meaning they are being tested in people. This reflects an extraordinary, global mobilization of resources.
What’s involved in testing a vaccine and how is the process being sped up?
It starts with testing in the laboratory and tests in animals before we move into clinical trials that involve people. With clinical trials, we start with Phase 1 studies. They involve a small number of people and help determine the vaccine’s safety and immune response. Normally that takes a year to 1½ years. In Phase 2 testing, the vaccine is given to a slightly larger pool of patients to continue to see if it is safe and well tolerated and to determine the best dosing schedule, and if the immune system is having the desired responses. Normally, that can last up to two years. In Phase 3 trials, we test the vaccine in thousands of volunteers for safety and to see if it is effective and protects them from infection or from severe cases of COVID-19 illness so that they’re less sick and less likely to transmit it to others. At this point, four vaccines are in Phase 3 trials in the United States.
None of the required steps are being skipped, but many are being done on a parallel timeline instead of one after the other. So instead of taking a few years, the studies can be completed in months. But the vaccines are still going through the very careful phases of testing and monitoring to make sure they’re safe, and many groups, including the Food and Drug Administration (FDA) and independent safety monitoring groups of experts, oversee the safety of each study in progress. Some companies have already begun to manufacture the vaccines, so they will be prepared to make more doses if the trials show they are safe and effective.
How would a COVID-19 vaccine work?
The fundamental concept is to teach the body’s immune system to recognize and fight off the virus when and if the body comes into contact with it. So when the body is exposed to the virus later, it mobilizes parts of the immune system — T cells and antibodies — to prevent infection or reduce the severity of the disease. Most COVID-19 vaccines contain copies of pieces of the virus that are made in the laboratory and delivered to the body to teach it to recognize the virus. Then the body can mount an immune response and be ready to attack when the real thing comes along.
What should we take away from recent news about Pfizer’s vaccine?
The announcement that the Pfizer vaccine was found to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection is very exciting and energizing news.
It’s important to keep in mind that these data are based on an early interim analysis by an independent group of experts. This early analysis, based on 94 individuals in the study (out of about 44,000) who developed COVID-19, compared how many cases occurred in the vaccine group and how many occurred in the placebo group. To make sure that these results hold up and to follow participants for safety, the clinical trial will continue to the final analysis. But 90% is a very good result and definitely higher than what we see from influenza vaccines, which are 40% to 60% effective.
It’s also important to remember that the vaccine is not FDA-approved yet. After the company submits an application for Emergency Use Authorization, the FDA will carefully review the safety and effectiveness data. But it is possible, if everything goes as planned, that this vaccine could have emergency authorization for certain high-risk populations before the end of the year. It will take some more time to make it available for the general public.
We will likely need more than one safe and effective vaccine, since there is substantial need and we must make sure we have enough options to protect different age groups and diverse populations. An important consideration is how vaccines are stored and distributed; the Pfizer vaccine has to be kept at very cold temperatures. And that’s another reason it will be important to have more than one option for different settings.
Which vaccines are being tested at NewYork-Presbyterian?
The vaccine being tested at NewYork-Presbyterian/Weill Cornell Medical Center is an RNA-based vaccine developed by the company Moderna and the National Institutes of Health. At NewYork-Presbyterian/Columbia University Irving Medical Center, we are doing a study to test the AstraZeneca/University of Oxford vaccine. It uses a weakened chimpanzee version of a common cold virus called adenovirus as a “carrier” to introduce a copy of a key protein of the SARS-CoV-2 spike protein so that when the body later encounters the SARS-CoV-2 virus, it remembers and attacks it.
Both campuses began testing the vaccines in people late this summer. ln the AstraZeneca trial, a voluntary pause was triggered in the United States to investigate a safety event that occurred in England. The study recently restarted after the FDA and an independent Data and Safety Monitoring Board completed a thorough review of all the safety data from trials using this vaccine and concluded it was safe to resume the study. Study pauses are not uncommon; they are a normal part of the clinical trial process and show that the careful oversight process is working. We will likely test other COVID-19 vaccines in the future.
Vaccine Delivery Systems
Almost all the COVID-19 vaccines being developed contain copies of what is called the SARS-CoV-2 spike protein, which is on the surface of the virus. The protein is like a key that unlocks receptors on human cells, allowing the virus to enter them and start infection. The hope is that the vaccine will stimulate production of antibodies that block the spike protein and prevent the virus from getting into cells.
COVID-19 vaccines use different strategies to deliver the virus to the immune system to prime it for an attack. Here are the main delivery methods and how they work:
- mRNA-based vaccines introduce a messenger RNA sequence — instructions for cells to build the SARS-CoV-2 spike protein — to trigger an immune response. The Moderna vaccine tested at NewYork-Presbyterian/Weill Cornell Medical Center uses this approach.
- DNA-based vaccines work by inserting synthetic DNA from the virus gene into a small DNA molecule called a plasmid. When the vaccine is injected into the body, cells incorporate the DNA plasmids and learn to build the SARS-CoV-2 protein in them.
- Viral vector vaccines use a virus, such as a common cold virus, that is inactivated and harmless. Genes of the SARS-CoV-2 spike protein are spliced into it. When the vaccine is administered, the protein prompts an immune response. The AstraZeneca vaccine uses this approach.
- Protein subunit vaccines introduce a fragment or portion of the SARS-CoV-2 spike protein into the body to stimulate the immune system.
How many vaccine doses will be needed to provide protection, and will it be effective for a lifetime?
We don’t yet know how long immunity (protection) after infection lasts, and we don’t know how long it will last after vaccination; it boils down to what kind of immune responses the vaccine is capable of producing. Most of the vaccines being studied right now, including both vaccines being tested at NewYork-Presbyterian, require two doses. Whether people will need an additional vaccine after that and if so how often, we don’t know yet. We don’t know how long the antibodies and other immune responses that someone develops from a vaccine will last and how long they will be protective.
What does the news that a few people, including a U.S. man, have been infected twice by the coronavirus mean for a vaccine?
The news about reinfection raises many important questions that are being actively investigated. For example, we don’t know how common reinfections are, but to date only a small number have been confirmed. We also don’t know how long immune responses last after SARS-CoV-2 infection and how these responses relate to protecting people from future infection. These pieces are key to understanding which immune responses will need to be stimulated by a vaccine to maintain protection. We believe that a vaccine is more likely to trigger the kind of immune response that’s protective against infection or severe illness than a natural infection with SARS-CoV-2.
Will one vaccine be effective for all groups of people?
In all these trials we want to make sure we have representation from individuals of all ages, races, and ethnicities in order to answer that question. This is important because we have such diverse patients and communities, many of which have been particularly affected by COVID-19. The same is true for individuals over the age of 65, because they are at high risk of getting infected with SARS-CoV-2 and having more severe illness. With the flu vaccine, for example, there are different formulations approved for use in different age groups.
What about pregnant women and children?
Pregnant women are not included in the current efficacy studies. That will come later. We need to understand a lot more about the risks and benefits of the vaccine before we administer it to pregnant women, and get more information to make sure their pregnancy won’t be affected. Pregnant women are a really important population to include in vaccine studies. In current Phase 3 trials, women who become pregnant during a study will be followed to monitor how they do. Children are not yet included in most efficacy studies. However, Pfizer recently received permission from the FDA to enroll children as young as 12 in its COVID-19 vaccine trial.
How many people will be recruited for these vaccine trials across the U.S. and what can participants expect?
Most Phase 3 studies will plan to recruit 30,000 to 45,000 people in the U.S. across multiple sites. We anticipate enrolling between 100 and 500 people for each trial conducted here; the Moderna trial at NewYork-Presbyterian/Weill Cornell and across the U.S. has been fully enrolled. Participants come to the clinic for the injections and are asked to monitor their symptoms afterward. We check in with them frequently to make sure they’re tolerating the vaccine well. We also collect blood samples to see if the body is developing the immune response we’re looking for. The study is “blinded,” meaning that neither we nor the participants know who got the vaccine and who got the placebo (an injection of salt water). The reason is to make sure that everyone’s symptoms are evaluated the same way, without bias, and that participants don’t change their behavior because they think the vaccine is protecting them. We don’t want anyone to assume they are protected from SARS-CoV-2, but to follow COVID-19 infection prevention guidelines and keep protecting themselves. Over time, we will see how many people become infected and, if they become infected, whether illness is less severe in those who received the vaccine compared to the placebo group.
What are the risks and the benefits of participating in a vaccine trial?
All vaccines have some risks. The common side effects — fever, chills, rash, aches and pains — usually go away within days, and most people go about their daily activities. Some risks are rare, such as allergic reactions like hives and difficulty breathing. There also may be risks we don’t know about, which is why we monitor volunteers so carefully. In terms of benefits, we tell people their participation may not directly benefit them, but it may benefit others in the future because of what we learn in the study. Many people want to contribute to this effort and are excited about the science and the cause, and enjoy helping their community.
How effective does a vaccine have to be to turn a corner on this pandemic?
Ideally, a vaccine would be more than 70% effective in preventing the infection. The FDA is saying that a vaccine that is safe and at least 50% effective could be considered for approval in the U.S. Such a vaccine would also be very beneficial to the individual and the community. A vaccine that is at least 50% effective means that at least 50% of the people who get it will be protected; even those who are not protected can benefit since it is possible the COVID-19 vaccine will make the disease milder for those who do get sick.
What happens to people in whom the vaccine doesn’t work or those who don’t get the vaccine?
We know that vaccines don’t just benefit the individual, but the wider community as well. When a large proportion of a community gets vaccinated and becomes immune to the disease, people who get the vaccine will be less likely to transmit the virus to others who were not able to get vaccinated, and the larger community will get some protection as a result.
Will an effective vaccine end the pandemic?
A vaccine will be an important tool in the toolbox and is critical in the effort to get our society and economy back on track. But it’s only one tool. We need to continue wearing masks, social distancing, and washing our hands. The hope is that we can reach a tipping point where we have a safe and effective vaccine, and enough people take it so that people are not getting infected anymore, and that takes time, likely toward the end of next year. The overall impact of a vaccine will depend on how many people are willing to take it after it is approved. So a return to normalcy will be gradual.
How optimistic are you that we will have an effective vaccine soon?
I am optimistic that one, if not more, of the vaccine candidates will be shown to be safe and effective, because there’s so much global effort and scientific investigation, and the studies are well designed. I think it is very possible we will have a vaccine ready for FDA review by the end of the year or early 2021. And that’s an important step; we also have to remember that making enough doses and ensuring equitable allocation and distribution of the vaccines are key steps in the process, and that may take some time.
Magdalena E. Sobieszczyk, M.D., MPH, is chief of the Division of Infectious Diseases in the Department of Medicine at NewYork-Presbyterian/Columbia University Irving Medical Center and a professor of medicine at Columbia University Vagelos College of Physicians and Surgeons. Her research focus includes HIV prevention strategies and clinical trials of HIV vaccines.
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