As flu season approaches and scientists continue to work on a vaccine for COVID-19, Andrea Amalfitano, dean of the College of Osteopathic Medicine and Osteopathic Heritage Foundation Endowed Professor of Pediatrics, Microbiology and Molecular Genetics, uses his expertise to shed light on how vaccines work and the process for creating new ones. The first of this two-part series addresses general questions about vaccines. The second part will address development of the COVID-19 vaccine.
How do vaccines work?
Vaccines work by introducing specific sub-portions, or antigens, of a desired “target,” like COVID-19, to the immune system in a manner that is safe and results in a training of the immune system should a vaccine recipient be subsequently exposed to COVID-19 naturally. The vaccinated individual will be able to ramp up an immune response that eliminates the COVID-19 much more rapidly than someone who was not vaccinated, thereby minimizing or completely preventing illness.
Our laboratories previously developed, for example, a vaccine platform for use against a variety of “targets.” This platform was created by genetically engineering a common cold virus to present antigens safely to the immune system. This unique vaccine platform has been safely used in hundreds of clinical trial participants targeting their cancers, and that safety record has allowed researchers to now test the platform’s ability to induce beneficial immunity against the COVID-19 virus in human subjects as part of an FDA-approved Phase I clinical trial.
Confirming safety is key, and at this time it is more critical than ever that FDA regulations are maintained and followed, as these will help confirm that an approved vaccine is both effective and safe. Suspending FDA regulations at this crucial time would be the last thing I would recommend, for example, to hasten the approval of any potential COVID-19 vaccine. Suspending FDA oversight would undermine the trust the public would have in any other vaccine, therapeutic, test or other medical device subsequently approved by the FDA.
We hear a lot about the fast-tracking of a coronavirus vaccine. What is the usual time frame for creating a new vaccine?
In my experience as a clinician/scientist who has developed new vaccine technologies for various purposes, the track typically is multiple years. Fast-tracking is not the typical term applied to vaccines, as the brunt of the time required to get a new vaccine approved is devoted to confirming the vaccine can be scaled up consistently and also has no untoward side-effects, especially when it is planned to be administered to potentially millions of people.
Given that, the annual flu vaccine is what I would consider a fast-tracked vaccine, as it is essentially a novel vaccine every year. The reasons it can be fast-tracked are: 1) the long-standing safety record (decades) of developing and producing flu vaccines using tried and true scale-up methods, 2) long-standing blood tests that consistently measure, and then correlate the amount of anti-flu antibodies generated by each annual flu vaccine with ultimate potential for efficacy.
What are the steps or phases of researching a new vaccine?
Typically, any new drug, vaccine or other form of medical therapeutic or device goes through three phases of clinical trials prior to receiving approval for generalized usage. Phase I studies typically involve dose testing and safety studies in normal human volunteers, as appropriate. Phase II studies involve using optimal doses of the new drug or vaccine in those potentially benefitting from the therapeutic, for example, a new drug to treat high blood pressure being evaluated in patients with high blood pressure. For flu vaccines, this phase would attempt to note how many anti-flu antibodies are produced by the potential new vaccine, and if these “antibody levels” are above the known thresholds required to have a “good” vaccine. Phase III studies typically involve testing the new therapeutic in trial subjects as compared to use of currently available therapeutics for the same disease indication to verify it is an improvement.
For flu vaccines, and more specifically COVID-19-specific vaccines, this phase may include asking clinical trial participants to receive a potential COVID-19 vaccine and monitor the rate of COVID-19 infection by these vaccine recipients over time. If the COVID-19 vaccine is “good,” those who receive the potential vaccine should have a much lower rate of acquiring COVID-19 infection than those trial participants who receive a placebo vaccine.
What are the risks associated with getting a new vaccine?
Vaccines are some of, if not the safest, types of medications doctors can provide to their patients. In fact, if you look back through time, beyond clean water, vaccines have saved more lives and decreased morbidity of the human race more so than any other medicine.
Risks can occur, as with anything administered to a human — even excess water consumption can be dangerous to humans. Clinical trials in hundreds or thousands of trial participants serve to identify potential side effects. Furthermore, many times the FDA will also add Phase IV studies, even after a new therapeutic or vaccine is approved, typically to monitor for very low-frequency side effects not identified in prior clinical trials.
Do vaccines have to be kept at a certain temperature to be effective?
This depends on the type of vaccine platform. Some can be dehydrated and/or delivered as an oral pill, while others may require refrigeration at specific temperatures to maintain viability. It is not clear what these viability requirements will be of the several potential COVID-19 vaccines currently being tested.
Obviously, this also has to be a consideration in regard to scalability. For example, if a vaccine can be delivered at room temperature and remain effective as an orally ingestible pill or tablet, this vaccine will be much more likely to succeed, versus a different vaccine that requires refrigeration until the time of a required administration.