How COVID-19 Vaccines Are Being Tested and Developed
By Dr. Jennifer Sedillo
Faculty Member, Public Health, American Military University
While new cases of COVID-19 are decreasing across most of the world, the threat from this deadly disease has not diminished. The virus is highly contagious and has a high case fatality rate, especially among older populations and those with pre-existing conditions. Many public health experts do not believe we will see an end to the pandemic and a return to normal social activities until a vaccine is produced and disseminated among the population.
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Vaccine discovery is a lengthy process that needs to be fully repeated for each new disease. Because each disease is unique in its biology and pathology, each vaccine must be uniquely designed.
But only experimental evidence in the form of clinical trials can demonstrate whether a vaccine is effective and safe. Some of the most important human diseases still do not have a highly effective vaccine approved for use, including Ebola, malaria and SARS-CoV.
COVID-19 Vaccine Trials Look Promising
However, there are positive signs that a vaccine can be protective against COVID-19. The fact that an antibody response is generated in humans who were previously infected by the disease is one sign. Another sign comes from animal trials in which monkeys that were administered the vaccine were found to be protected against infection from the virus.
Globally, as of May 5, there were eight vaccines in clinical trials and 100 candidates in preclinical trials for COVID-19. Of these eight vaccines in clinical trials, seven were going through Phase 1 and 2 trials while one was in a Phase 1 trial. The first two phases of clinical trials typically are used to show the safety of the vaccine in humans and proof of principle that an immune response is generated.
Typically, Phase 1 is conducted in a population that is not at actual risk of the disease. In the current Phase 1 trials, the subjects are males and non-pregnant females in generally good health. During these phases, the participants’ production of antibodies is also examined.
Phase 2 trials involve larger numbers of participants and include those at high risk for the disease (such as emergency medical workers and healthcare providers). Phase 3 will look at the efficacy of the vaccine, meaning its ability to protect against disease as well as the potential for rare side effects.
Determining the Most Effective Vaccine Type
The type of vaccine developed varies based on the disease it is targeting. Vaccine types are divided into categories based on how they are produced and in what form the antigen is presented in the vaccine. Interestingly, only three of the current eight COVID-19 vaccines now in human trials are using an inactivated vaccine type which has previously been approved for use in humans and is in current use in the U.S.
Three inactivated vaccine candidates are in trials. Inactivated vaccines are currently used for a wide array of diseases including hepatitis A, flu and polio. They work by injecting the killed virus into the body so that the immune system can recognize it and make antibodies to the virus. Typically, multiple doses of inactivated vaccines are needed to elicit a strong immune response.
The other vaccine types currently being investigated in COVID-19 human trials consist of DNA vaccines, RNA vaccines and vector vaccines. At present, there is only one approved human vaccine that uses any of these platforms for producing a vaccine type. While scientists have studied these vaccine types for some time in clinical trials, traditional vaccine types are the most common types used in the U.S. today. The advantages of the new vaccine types are efficiency, low cost of production and a robust immune response.
New Vaccines Work by Injecting Genetic Material into the Body to Produce Antigens
DNA vaccines work by injecting a circular piece of DNA (plasmid) directly into the muscle. The cells then take in the DNA and process it as they would our own DNA, which means transcribing it into RNA and translating it into protein. The protein produced would be both the antigen and adjuvant needed to produce an immune response. For this vaccine, the DNA must enter the nucleus of the cell.
The safety of this vaccine hinges on the DNA not integrating into our cells’ DNA but staying separate. In trials, the vaccine shows a robust response; however, the only such approved vaccines are for use in dogs and horses.
RNA vaccines are similar to DNA vaccines except they can skip a step in the protein-making process (transcription); also, they do not need to enter the nucleus of the cell. The mRNA (messenger RNA) vaccine can readily be absorbed by cells and translated into proteins (antigens).
The advantages of RNA vaccines are they can produce both an antibody response and a T-cell response that not all vaccine types can produce without the potential to cause disease. That’s the case with live vaccines. While no RNA vaccines have been approved for human use, they have shown safety and efficacy in human trials for diseases, including cancer.
Vector vaccines use a similar process to DNA vaccines but use a weakened virus (such as adenovirus) to deliver the DNA into the body and cells. The current COVID-19 candidates are using a non-replicating vector, which is thought to be safer than a replicating vector.
Vector vaccines have been studied in clinical trials for Ebola, Zika and MERS, among other diseases. Recently, a vaccine for Dengue fever was approved for use in the U.S. But the scope was limited to “individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas.”
It’s Possible that Multiple Vaccines Will Be Approved for Use against COVID-19
It is too early to predict which, if any, of the current vaccine candidates will be successful. But it is possible that multiple vaccines for COVID-19 will be approved. Companies involved in clinical trials are looking ahead and ramping up their production capabilities as well as making strategic partnerships to enable efficient production of large amounts of the vaccine.
The hope is that if Phase 3 trials can show efficacy and safety, the Food and Drug Administration will grant the vaccine Emergency Use Authorization to begin vaccinating the population. Once a vaccine is approved, a plan will need to be adapted to provide the vaccine to the population in the fairest and most equitable way.
About the Author
Dr. Jennifer Sedillo has been a faculty member of Public Health at American Military University since receiving her doctorate in Public Health from the University of South Florida in 2014. Her expertise is in infectious disease research and microbiology. Her publications focus on cellular and molecular biology of infectious disease microorganisms. Her current research interests focus on foodborne illnesses and using social media to improve health education to the general public.