Present By Alan M. Preston, MHA, ScD

COVID-19 Vaccination Overview:

From the Beginning to Present

By Alan M. Preston, MHA, ScD

The virus that causes COVID-19 is related to other coronaviruses. The good news is that scientists have been studying coronaviruses for years and there is a lot we have learned. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are not new, and vaccinations have been developed for previous strains. Nevertheless, each strain requires a specific vaccine to combat the RNA makeup of such strain in order to be an effective vaccine. Currently, there are three approved vaccines:

1. Pfizer-BioNTech: for ages 12 years and older and needs 2 shots given 3 weeks (21 days) apart.

2. Moderna: for ages 18 years and older and needs 2 shots given 4 weeks (28 days) apart.

3. Johnson & Johnson’s Janssen: for ages 18 years and older and needs 1 shot.

Vaccines go through three phases of clinical trials to make sure they are safe and effective. For other vaccines routinely used in the United States, the three phases of clinical trials are performed one at a time and do not overlap, which is why the standard process is so lengthy. The third phase usually takes the longest. During the development of COVID-19 vaccines, these phases have overlapped to speed up the process. No trial phases have been skipped. These three preliminary clinical trials must be performed to obtain approval from the FDA:

1. Phase I Vaccine Trials

This first trial involves a small group of adults, usually between 20-80 subjects. If the vaccine is intended for children, researchers will first test adults and then gradually step down the age of the test subjects until they reach their target. This is one reason that the age limits for children are in place. The goals of Phase 1 testing are to assess the safety of the candidate vaccine and determine the type and extent of immune response that the vaccine provokes.

2. Phase II Vaccine Trials

A larger group of several hundred individuals participates in Phase II testing. Phase II testing aims to study the individual vaccine’s safety, efficacy, proposed doses, schedule of immunizations and delivery method.

3. Phase III Vaccine Trials

Successful Phase II candidate vaccines

move on to more extensive trials, involving thousands to tens of thousands of people. One Phase III goal is to assess vaccine safety in a large group of people. Specific rare side effects might not surface in the smaller groups of subjects tested in earlier phases.

Recall that the J&J vaccination was suspended for a short period when some people developed blood clots. At the time of the discovery, J&J had administered over 7 million vaccinations, and six of those people vaccinated presented with a blood clot. As in all clinical trials, there are often reported side effects. The question, which takes time to answer, is whether or not the side effects were the cause of the vaccination or simply a coincidence after taking the vaccination. Furthermore, even if the vaccine "caused" a potential side effect in a small population (.00008571% of the J&J population indicated a blood clot after the vaccine), the number of lives saved by providing the COVID-19 vaccine may be seen to outweigh the preventable side effect seen in the J&J vaccine. The FDA will continue to monitor the efficacy and production of the vaccine. Results from these trials have shown that COVID-19 vaccines are effective. They have also demonstrated no serious safety concerns after many weeks following vaccination. This is an important milestone, as it is unusual for adverse effects caused by vaccines to appear after this amount of time.

Myths of the vaccine exposed

Anytime there is a new drug or vaccine, people are skeptical as to the long-term effects. There is no shortage of conspiracy theories about the new vaccines. One of the more prevalent myths is that the Pfizer and Moderna vaccines introduce the RNA of the virus, which will alter the DNA of the host. According to the CDC, mRNA vaccines work by instructing cells in the body how to make a protein that triggers an immune response. Injecting mRNA into your body will not interact nor do anything to the DNA of your cells. Human cells break down and get rid of the mRNA soon after they have finished using the instructions.

The manufacturing ability of our cells extends beyond human proteins. When we are infected with a virus, including relatively harmless viruses like those that cause the common cold, these invaders inject their genetic material into our cells, resulting in pieces of mRNA encoding viral proteins being sent to our protein-making machinery. Doing so enables the virus to assemble new viral particles out of these proteins and spread. Although mRNA vaccines are a relatively new technology, they are based on the same ancient premise: delivering mRNA into our cells, which they will use to manufacture a viral protein. mRNA vaccines don’t carry enzymes like an HIV virus, so there is no risk the genetic material that the SARS COVID19 virus contains could alter our DNA.

The delivery systems of both the Moderna and Pfizer vaccines are brilliant. Here is how it works. First, the scientist takes a lipid nanoparticle to introduce the mRNA into a protective casing. To maintain the integrity of the lipid nanoparticle, the manufacturing process must keep it very cold (between -76 and -112 degrees Fahrenheit); otherwise, the efficacy is lost in a few days of the vial of the vaccine. This creates a transport vehicle to introduce to the human hosts. The COVID19 S-Protein is contained in the lipid nanoparticle. Once it gets into the host cell, the good news is that it does not enter into the cell's nucleus, where the cell's DNA is located. It is a brilliant transport mechanism and, in my opinion, safe.

Definitions of science

According to one definition, "Science is any system of knowledge concerned with the physical world and its phenomena, and that entails unbiased observations and systematic experimentation." In general, science involves a pursuit of knowledge, and there are always limitations present when studies are performed. And, as new data become available, the conclusion of the observations may change slightly, significantly or not at all. Physicians have numerous observations as to what appears to be effective and what appears to be less effective. True science allows conclusions that are based upon observations to be examined. We are still learning about COVID-19; however, we have millions of data points that we previously did not have. The science should evolve to better understand COVID-19 and the vulnerable populations that are susceptible to it. Those over age 70 with comorbidities are far more vulnerable than those under 60 with minor health problems when acquiring COVID19. We should treat each person as an individual and determine which individuals need special protection. Individuals in a population are generally at very low risk of dying from such a disease and act accordingly.

Doctors should be given a broad latitude to practice medicine based on the evidence of each patient. As I always say, "be careful what conclusions you come to based upon a study or the underlying data." There are always limitations to all studies, and the generalization of any research also has limitations when one tries to generalize beyond the scope of the study.

Alan Preston, MHA, ScD works in the area of Population Health Management and has a doctorate in Science in Epidemiology and Biostatistics from Tulane University and has spent his entire career in the health care space.