Vaccines are made of antigenic components, along with other chemicals that increase its efficacy, such as adjuvants and preservatives.
Since Edward Jenner first discovered vaccination in 1769, this breakthrough has saved countless lives. Before Jenner’s vaccine against smallpox was implemented, as many as 400,000 people died of the disease, annually, in Europe alone. The traditional treatment against the disease—variolation—involved taking a sample from a smallpox patient and injecting that into someone who was susceptible to contracting the disease. Variolation was risky, given that traditional medics were knowingly inserting the smallpox virus into another patient. If the dose was too high, the patient might face the full force of the disease. Jenner’s vaccine, on the other hand, adopted a similar technique, but one that was significantly safer.
Edward Jenner’s vaccine was born from the observation that milkmaids who had previously contracted cowpox didn’t get smallpox. Jenner decided put this tall tale to the scientific test. He injected an 8-year-old boy with the cowpox disease. After the boy recovered from cowpox, Jenner then infected the boy with smallpox. The boy did not contract the disease, as he had become immune to it. This simple vaccine began a healthcare revolution in the world that continues to this day.
We’ve now discovered a broad range of ways to achieve immunity against diseases. Jenner’s strategy is now one prong in a weapon that has widely diversified through years of curiosity and scientific inquiry. So… what strategies of vaccination are available to us today?
To understand what goes into a vaccine, and appreciate the nuance of our modern developments, it is important to understand how the body gains immunity against diseases.
Immune Response And Memory
The immune system reacts to pathogens (or any other foreign particle) in two broad ways. The first is the primary response, where certain immune cells will indiscriminately attack anything that they identify to be foreign. If this fails to nullify the threat, the immune system calls upon its more specialized troops, which marks the start of the secondary response.
In the secondary response, T-cells and B-cells are recruited to handle the threat. B-cells will produce antibodies—chemical death tags that signal to T-cells and various other immune cells to finish killing anything tagged with the antibody. This system is extremely efficient, but crucially for vaccination, it can remember past infections from pathogens. If the same pathogen enters the body again, the immune system is able to fight and finish it off faster.
Therefore, a vaccine can be anything that gives the immune system the long-term capability to fight off a given disease.
This leads us to the key ingredient in a vaccine—the one that gives the immune system the memory of a pathogen it has not yet fought.
There are various ways to develop this immunity, as will be explained below.
Live attenuated vaccines
A live attenuated vaccine is the route Edward Jenner’s cowpox vaccine followed. Attenuated live vaccines, as the name suggests, are live pathogens that have been weakened so they can no longer cause the disease, but still manage to stimulate the immune system. This stimulation leads immune cells to develop memory of the disease.
The weakened pathogen can be a non-pathogenic or less pathogenic species or variant of the disease-causing organism. The cowpox virus Jenner used belonged to the same family as the smallpox vaccine—the poxviruses—and therefore shared similar molecular markers that the immune system responded to in order to fight the disease.
So far, live attenuated vaccines have been some of the most successful vaccines in history. These vaccines create the longest memory against a pathogen; in many cases, people only require one vaccination for it to provide nearly lifelong immunity against the disease. Vaccines against smallpox, measles, and chickenpox, just to name a few, have all used live attenuated vaccines.
If a live attenuated pathogen is considered unfeasible for a disease (due to safety, side effects, or difficulty to create a safe variant), a dead or inactivated pathogen is injected.
The pathogen is killed, either through heat or chemical treatments and then injected into the body. Since the pathogen is still a foreign substance and carries all the pathogenic markers, called antigens, it is able to generate an immune response and induce memory formation.
These aren’t as effective as live vaccines in terms of giving immunity to the body, so one usually has to take multiple shots of the vaccine, called boosters.
Subunits, DNA and genetic engineering
Then there are vaccines where the whole pathogen isn’t injected. Instead, we break down the pathogen, identify the antigens on the pathogen and then only inject those molecules into the body. The antigen might be a sugar molecule on the pathogen, a specific protein, or, as in the cases of a virus, only its capsid. We can inject a combination of these molecules in inventive ways to stimulate the immune system in the exact way we want.
There are also DNA vaccines. Here, instead of injecting the antigenic molecule itself, the DNA that codes for those molecules is injected. Some host cells will express the antigen code in the DNA (this is an anomalous, yet normal behavior of host cells), which will lead to immunization.
Besides these, there are newer vaccine technologies involving various genetic engineering techniques to make vaccines safer and highly precise instruments to defeat diseases like cancer and HIV.
Adjuvants, preservatives and more:
Vaccines aren’t only made of the weakened pathogen or antigens in a water solution. There are adjuvants, preservatives, stabilizers, antibiotics and more to ensure that the vaccine has the best chance of working in the body. Vaccine designers carefully concoct the perfect formula that will aid the immunogenic part of the vaccine to do its thing.
This is also the area that has been most widely discussed both in the media and in conspiracy theory circles. Chemicals used for adjuvants, molecules that boost the immune-conferring properties of the vaccine, have come under scrutiny for their potential to be toxic to the body.
Aluminum compounds are an oft-used adjuvant. These have raised toxicity concerns in the public. Furthermore, thimerosal, a mercury-based adjuvant, was banned by the FDA over health concerns. Though such compounds are toxic to the body, their amount in the formulation is too minimal to cause any serious side effects.
With that being said, adjuvant research is addressing potential health concerns and attempting to formulate molecules that are safer and more efficacious than molecules used in the past.
Since Jenner’s cowpox ‘eureka’ moment, vaccines have saved millions of lives over the years. In this time of Corona, there are a host of new technologies being tested out, such as mRNA vaccines, as well as adjuvants designed through recombinant technologies. These new strategies provide hope for a potential cure for viral diseases that continue to ravage large parts of the global population.