Hundreds of companies worldwide are scrambling to develop a vaccine for the SARS-CoV 2 virus, better known as COVID-19, but as the pandemic progresses, many people are beginning to doubt the possibility, safety, or effectiveness of the vaccine. In fact, according to a survey done by The Harris Poll on behalf of the American Osteopathic Association, more than 45% of adults have doubts about vaccine safety, and this can have serious effects on the public health, as family medicine specialist Dr. Paul Ehrmann states, "Some diseases, like measles, require as much as 95 percent of the population to be vaccinated in order to achieve herd immunity." Yet, how do vaccines actually work, and how do federal agencies prevent dangerous drugs from getting onto the market?
Vaccines were invented in 1796 by Edward Jenner, who is often considered the father of immunology, when he innoculated a 13 year-old with the cowpox virus, causing the boy to gain immunity to smallpox. This is because when the body is first infected by a pathogen, it takes immune cells several days or weeks to fight the infection. However, when the body comes in contact with the same pathogen again, the immune system remembers how to fight the pathogen because of T-lymphocytes, also known as memory cells, so the immune response will be much quicker. Vaccines work to imitate the infection and activate an immune response by using a weakened form of the pathogen, so when the body encounters a more virulent form of the pathogen, the immune system will be ready to defend the body. By 1979, smallpox was declared to be eradicated globally, and many more diseases that had extremely deadly throughout history were also eradicated.
This graphic compares some different types of vaccines! Image Source
However, while most vaccines are administered through injection, orally, or through the nose, those vaccines actually come in different types. These vaccines are designed to introduce a weakened form of the pathogen into your body to cause an immune response, which allows your adaptive immune system recognize the pathogen if you come in contact with it again. One type of vaccine is the live-attenuated vaccine, which uses a weakened form of the pathogen and one or two doses can give you immunity for a lifetime. These vaccines are commonly made by growing the pathogen in many different cell cultures or animal embryos, so the pathogen becomes better at replicating in an animal cell, but not a human cell. After growing through nearly 200 different cell cultures, the pathogen loses its ability to grow in a human cell, and while the immune system can still recognize it, the pathogen will not be able to replicate well. A common concern with this type of vaccine is that since the pathogen was developed by evolving the pathogen into a weakened form, there is a small risk that it can mutate back into a pathogenic form, such as with the oral polio vaccine (OPV). However, this is unlikely because the weakened pathogen typically has limited ability to replicate in the cell, which reduces its chances of evolution. Another type of vaccine are inactivated vaccines, which typically includes flu shots, that use the killed pathogen, so multiple doses may be required since these vaccines don't provide as much immunity as live-attenuated vaccines. These vaccines are typically made by killing the pathogen through heat or chemicals, like formaldehyde, so the pathogen will not be able to replicate. This reduces the risk of mutations, since the pathogen cannot replicate at all.
However, some vaccines aren't targeted towards the ability for a pathogen to replicate, and instead, vaccines such as subunit, recombinant, polysaccharide, and conjugate vaccines target a specific part of the pathogen, such as the protein or capsid. Subunit and recombinant vaccines are made by creating a specific protein from the pathogen rather than the entire pathogen, whether that's through isolating the protein or genetic engineering, which provides immunity for a targeted part of the pathogen when the immune response occurs. Conjugate vaccines are similar to subunit vaccines, since they are made of two different parts, but conjugate vaccines are composed of a polysaccharide antigen combined with a carrier molecule, while in polysaccharide vaccines, only the capsule of the bacteria is used to activate the immune response. Yet, some diseases aren't caused by the pathogen itself, but the toxins produced by the pathogen, so toxoid vaccines are weakened or inactivated toxins produced by the pathogen that is administered to induce an immune response against the toxin rather than the pathogen. This is done by inactivating the toxic through heat or chemicals, and additional doses will typically be required to gain long-term protection against disease.
Yet, if the purpose of the vaccine is the same, why are there so many types of vaccines, especially since some types work better than others? When scientists develop vaccines, it is important to consider factors such as how the immune system responds against the pathogen, the targeted population, and the most effective approach for creating the vaccine. Scientists also need to take into account some practical considerations, since some vaccines, such as live-attenuated vaccines, are temperature sensitive, and this can prove to be a problem when transporting vaccines to different parts of the world. However, live-attenuated vaccines do not require multiple doses, unlike some other vaccines, so this may be more convienent for people who do not have regular access to medical care. In addition, since some vaccines cause mild symptoms of the disease, people with weakened immune systems, long-term health issues, or people that have had an organ transplant may have a higher risk of contracting the disease because of the live pathogens within live-attenuated vaccines, whereas subunit, recombinant, polysaccharide, and conjugate vaccines can be used on most people.
This was the "vaccines cause autism" paper that was retracted! Image Source
Despite the widespread success of vaccines, the vaccine industry began to decline in the 1970s and 1980s due to decreased profitibility and an increased risk of prosecution. While the industry has recovered due to the introduction of the National Vaccine Injury Compensation Program in 1986, this has left an impact on vaccines today, as they have met resistance from the public. To illustrate, since the invention of vaccines, vaccinations for common diseases, such as measles, mumps, and rubella, are usually required for children. However, in a flawed article published in Lancet from 1998, researchers found that the measles, mumps, and rubellas (MMR) vaccine that are required for children in the United States caused intestinal inflammation that led to harmful proteins entering the bloodstream, subsequently entering into the brain and causing autism. This led to concerns from the public about the safety of vaccines, although the study was later retracted because the researchers did not study the incidence of autism in children that did not get the vaccine, and the symptoms of intestinal inflammation were only observed after the symptoms of autism. However, the study left a lasting impact on the public, as currently, around 13% of parents believe that the measles vaccine is unsafe, according to a study by Pew Research Center.
This graphic shows the drug development process! Image Source
This raises the question about how are vaccines developed and tested. In the United States, all vaccines must be approved by the Food and Drug Administration (FDA) to ensure the safety, effectiveness, and availability of the vaccine. This was established after tragedies such as the Tuskegee Syphillus Experiment, Lash Lure, and St. Louis Tragedy, which occurred due to the lack of regulation in drug development. There are many stages to the drug development process standardized by the FDA, which includes the stages Exploratory Stage, Pre-Clinical Stage, Application, Phase I, II, and II Clinical Trials, and Post-Licensure Monitoring. First, vaccine development starts in a laboratory during the Exploratory Stage, where scientists conducts research to discover antigens, vaccine types, and methods that work best against certain pathogens. If a vaccine candidate performs well during the Exploratory Stage, it will be tested on animals and cell cultures during the Pre-Clinical Stage to determine the safety and effectiveness of the vaccine. After that, if the vaccine succeeds, it will proceed to the Application Stage, where the company will submit an Investigational New Drug (IND) Application to the FDA and review board to approve. This application will detail testing, manufacturing, reports, and the proposed clinical trials. If the vaccine has been approved, it will enter the Phase I Clinical Trials, where a small group of around 20-100 people will be given the vaccine to test for safety and see if the vaccine is effective against the pathogen, occasionally by exposing the test participants to a modified form of the pathogen. If researchers receive satisfactory results, the vaccine will move on to Phase II Clinical Trials, where a larger group of people will receive the vaccine to test for safety, effectiveness, and possible methods of delivery, while comparing the results with a placebo group. In the Phase III Clinical Trial Stage, over 10,000 participants will be tested with the vaccine using a double-blind and randomized trial with a placebo group. With a larger group of people, some rare side effects may appear, which may not have been discovered beforehand. Finally, after many satisfactory trials, the vaccine may be submitted through a Biologics License Application to be approved by the FDA. Many factors will be taken into account when approving a vaccine, such as the production and efficacy of the vaccine. However, once a vaccine has been approved, the process isn't over yet. Manufacturers will have to continuously test for side effects to ensure the safety of the population, and the vaccine development process can often take more than 10 years.
With the invention of vaccines, this has saved millions of lives as diseases that were previously deadly have now been eradicated. However, many people are still uncertain about the safety of vaccines, because despite the rigorous testing and standards set by federal agencies, some unsafe vaccines do make it on to market. However, vaccines are crucial for public health and prevention of disease, so by providing publicly available information, education, and resources about vaccines, we can help promote health and well-being for all.
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