The coronavirus disease 2019 (COVID-19) vaccines that are leading the pack are utilizing a new vaccine technology that has never been approved for human use by the FDA. As a result, there are a lot of unknowns.
There are currently more than 160 different vaccine candidates in the pipeline to protect against SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The COVID-19 vaccines that are leading the pack are utilizing a new vaccine technology that has never been approved for human use by the FDA.
In a free, 1-hour webinar from MJH Life Sciences™, the parent company of The American Journal of Managed Care®, 3 top experts discussed vaccine development, the latest clinical trial evidence, and the future of COVID-19 vaccines. Did you miss the webinar? You can still register for free and watch the video on demand.
Angela Rasmussen, PhD, associate research scientist, Center for Infection and Immunity, Mailman School of Public Health, Columbia University, kicked off the discussion with a history of vaccine development and the COVID-19 vaccine pipeline.
She explained that there is currently 1 vaccine approved for limited use that was developed for use in China's military, and then there are several vaccines that have begun to move into phase 3 clinical trials. At the time of the webinar, there were more than 140 preclinical vaccines, 18 in phase 1, 12 in phase 2, and 6 in phase 3.
Historically, there were 4 vaccine platforms: cross-protection, toxoid, inactivated, or live attenuated forms. Rasmussen explained that all of these platforms have advantages and disadvantages, but that they all have “major public health benefits.”
“It’s important to note that all of these different vaccine strategies have really been game changers for public health,” she said.
The oral polio vaccine developed by Albert Sabin, MD, used live attenuated strains of the poliovirus, while the vaccine developed by Jonas Salk, MD, used inactivated virus. The disadvantage to these traditional vaccine approaches is that they can be more challenging to manufacture at scale, Rasmussen said. Another problem is that there is a risk of reversion to a virulent form.
With the realization that there needed to be new approaches to address the safety and efficacy concerns of vaccines, new technologies were developed:
RNA/DNA vaccines are leading the pack for the COVID-19 vaccines being investigated.
“This is basically taking the DNA or the RNA that codes for the antigen and introducing it into your cells itself and then letting your cells basically do the heavy lifting and producing that protein that your immune system will recognize as foreign,” Rasmussen explained. “And this is desirable because they're, they're fast and easy to make. They're inexpensive to manufacture with our current nucleic acid synthesis technologies.”
Gregory A. Poland, MD, MACP, FIDSA, FRCP, Mary Lowell Leary Emeritus Professor of Medicine, Infectious Diseases, Molecular Pharmacology, and Experimental Therapeutics; distinguished investigator, Mayo Clinic; director, Mayo Vaccine Research Group; and editor-in-chief, VACCINE, discussed principles, prejudices, and what he called “porcupines.”
“You can have your own opinions but not your own facts,” he said. “Science is not a democracy.”
The principles are those “hallmarks of science”: repeatability, generalizability, and peer-reviewed results, as well as an environment that is open to inquiry and a willingness to question dogma.
He described the “porcupines” as hurdles of vaccine development, such as public concerns over Operation Warp Speed, the perception of cutting corners, how the vaccine will be allocated, and the cost of the vaccine. There have also been profiteering concerns.
Poland pointed out that there have been 3 novel coronaviruses that have crossed the species barrier to infect humans in the last 16 years. In addition, there was an influenza pandemic at the beginning of the century and multiple national and global exercises have been in place.
“So, we have no excuse for not being ready, prepared, and in sync,” he said. “And while this may have been a shock, COVID-19, it should not have been a surprise.”
The unknowns of a COVID-19 vaccine include how long immunity will last. With seasonal human coronaviruses, immunity can last anywhere from 80 days to a few years, and the studies are showing different lengths of time. As a result, no one knows what the true durability of a vaccine will be.
Ideally, a vaccine would produce immunity after a single dose—one of the vaccines in phase 3 needs 2 doses—and provide long-lasting durable protective immunity. Poland is expecting multiple vaccines will be released. He predicts a 2-dose vaccine will be realized in January, but that a more effective 2-dose vaccine that has a lower rate of adverse events (AEs) will be released a few months after that, and another 2-dose vaccine with an even lower rate of AEs will be released after that, and finally a fourth vaccine that only requires 1 dose will make it to market with a very low rate of AEs and the highest efficacy.
“My point is that these are going to roll out possibly through different mechanisms over several months,” Poland said.
Finally, the moderator, Walter A. Orenstein, MD, professor and associate director, Emory Vaccine Center; professor, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine; and director, Emory-UGA Center of Excellence for Influenza Research and Surveillance, discussed how to optimize the impact of future COVID-19 vaccines and provided implementation recommendations.
“One of my favorite quotes is ‘vaccines do not save lives; vaccinations save lives.’ And a vaccine dose that remains in the pile is 0% effective no matter what the results of the clinical trial were,” he said. “Our goal is to get those doses into people for whom they're recommended.”
Orenstein explained that there remain a number of questions that need to be answered in order to rollout a vaccine. Since we will not have access to 330 million doses on day 1 after a vaccine becomes available, the country will have to make decisions about which individuals get priority access. Right away, we might not have much information on the durability of a vaccine. Another unknown is the risk factors for vaccine failure and if it might be remedied by extra doses. Finally, there is the potential for vaccine AEs, but we may not have a good idea of those AEs after widespread use.
To address some of these issues and unknowns, Orenstein said that the country will have to set up a monitoring system for safety and effectiveness in the long term and priority groups will need to be identified. The highest priority will probably be given to health care and essential workers, which could be as many as 122 million people. The remaining population accounts for more than 200 million people. Both of those groups will likely need to be tiered as doses become available.
Orenstein recommends clinicians follow guidance from the Advisory Committee on Immunization Practices, urge their high-risk population patients get vaccinated, report AEs to the Vaccine Adverse Event Reporting System, and continue to report COVID-19 cases.
Ensuring uptake is an important question that someone in the audience asked. Removing barriers to access is the first thing that needs to be done, and cost is one of the barriers that needs to be removed. But vaccines also need to be made convenient. Finally, people who have doubts need to be reassured. There is a high proportion of people who are currently saying they don’t want to get the vaccine.
“We need to convince them, and that means we need to have the resources to communicate and overcome their hesitancy,” Orenstein said. “Often health care providers play a major role in vaccine hesitancy issues.”