What are the mechanisms behind vaccines?
Vaccines prevent up to 3 million deaths each year and create herd immunity that protects unvaccinated. What are the different types of vaccines, and how do they work?
Why do we need vaccines?
Today humanity can prevent 29 diseases with vaccines. Fourteen of these diseases are almost forgotten and appear very rarely, thanks to herd immunity after mass vaccination. These are:
- hepatitis A and B
- Haemophilus influenzae type B
- whooping cough
- pneumococcal infection
Humanity has already eradicated some of the diseases. For example, smallpox caused by Variola minor had killed more than 500 million people in pre-vaccination times, but mass vaccination eradicated it in the 20th century. How was it possible?
A vaccine acts specifically against a particular pathogen. Each pathogen contains antigens—the particles recognized by the immune system that reacts by producing antibodies.
Antibodies bind to antigens and thus mark them as targets for an immune response. Then, immune cells start destroying pathogen cells. So, here are at least two steps: to recognize the enemy and destroy it.
Because of containing pathogens or antigens, vaccines provoke the immune system to respond.
Vaccines usually have one of the following:
- inactive pathogen
- weakened pathogen
- deactivated pathogen toxins
- purified antigens from the pathogen
In other words, vaccines contain parts of the pathogen or even whole pathogen cells. These pathogens are present in harmless doses or modified to cause no illness. Thus, they make our bodies produce antibodies before we meet an active pathogen of this kind in our daily life.
What kinds of vaccines are there?
Vaccines differ by their contents. They can contain:
- a dead pathogen
- a weakened pathogen
- DNA or RNA strands of a pathogen
- isolated parts of a pathogen
- a different virus (a vector) modified to induce a similar response
Vaccines that contain dead viruses or bacteria are inactivated or killed vaccines. To inactivate a pathogen, researchers use heat or chemicals like formaldehyde. A virus or bacteria treated in such a way can’t replicate anymore and cause infection.
There are also vaccines containing weakened live pathogens. Such vaccines are called attenuated. These are more effective because they produce more potent and long-lasting effects. They are more widely used than inactivated ones, although with precaution to patients with immunodeficiency. Older adults are often advised to use inactivated vaccines because of their weakened immunity. So are pregnant women.
Above is an artist’s impression of variola, the virus that causes smallpox. It was one of the first documented targets of immunization attempts several centuries ago.
Let’s see how they make live attenuated vaccines.
Vaccine producers lessen the pathogen’s infectious properties by genetically modifying it or introducing it into the environment where changes will happen naturally. In the latter case, a basic evolution principle works.
To be weakened, viruses that affect people are cultivated in other environments—animals, tissue cultures, or animal embryo cells. The virus gradually loses its efficacy against humans after several reinfections in these environments because the selection pressure works against it.
A virus that undergoes selection loses its ability to cause acute infections in humans, and these same viruses are used in vaccines. Live attenuated vaccines are harmless because a healthy human immune system easily copes with weakened viruses in low dosage.
This type of vaccine works against both viral and bacterial infections. Weakened vaccines can cause a life-long presence of antibodies. That’s why some vaccines are administered only once.
The smallpox vaccine is a famous example of a live vaccine. The method of immunizing with live pathogens was invented, according to written sources of the 15th century, in China, later in India, and then reinvented in the late 18th century by an English physician Edward Jenner. He observed that milkmaids were resistant to smallpox. It led Jenner to think that something that causes cowpox in cows can induce immunity to smallpox in humans.
Edward Jenner scratched cowpox material onto the skin of an 8-years son of his gardener. The boy had a fever but recovered shortly and showed no more symptoms. Then, Jenner infected him with smallpox taken from an infected woman. The boy appeared to be resistant to this illness.
The practice of inducing immunity against smallpox was called variolation—the term derived from the name of the pathogen, Variola major. Variolation was widely practiced in Europe in the 17th century and reacher as far as the Russian Empire. In 1769, empress Catherine the Great got variolated by British physicians and her 14-year-old son Paul and about 140 members of the court. The term vaccination appeared later and borrows from Jenner’s experiments with cowpox: in Latin, vacca means a cow.
DNA and RNA vaccines
One of the most up-to-date types of vaccines are vaccines based on the genetic sequence of a pathogen. Crudely speaking, virus bodies are essentially DNA or RNA sequences protected by a layer of proteins. Therefore, a vaccine encoding a pathogen can contain a DNA or RNA sequence, respectively.
Vaccines based on nucleic acids make the immune system respond by synthesizing antibodies—just like the two types of vaccines you already know. The difference is that no attenuated or dead pathogen participates in the process.
DNA and RNA vaccines makers take the part of the sequence necessary for provoking an immune response. Our immune system reacts to whole pathogens and their components—proteins or genetic materials called antigens. Thus, a vaccine based on nucleic acid will provoke one’s immune system without a threat of infection.
Another strong argument for this type of vaccine is fast development. The vaccines based on pathogens are very time-consuming because cultivating a weakened virus takes time. Producing a DNA or RNA-based vaccine is possible after decoding the necessary part of the nucleotide sequence. Cloning and amplifying genetic sequences are pretty straightforward tasks for scientists today. Also, protein structures are much more complicated than genetic sequences. Thus, vaccines made of pathogenic proteins need more time too.
One of the most promising modern vaccines is the vaccine against COVID-19 produced by Pfizer and BioNTech. It is based on messenger RNA (mRNA). COVID-19 is an RNA virus, and mRNA is a molecule describing proteins that activate the immune response to this virus. When mRNA is in the body, our cells start building proteins according to its instructions, and the immune system reacts to them.
In the case of a DNA vaccine, it would take more time for the immunity to react because DNA-based viruses use the capacity of the cells they infect to build an mRNA and then make proteins according to instructions. Therefore, in the case of a DNA vaccine, another step is added to the processes that happen in our cells.
Along with DNA/RNA vaccines, there are two more types of innovative vaccines. Let’s look at them.
Viral vector vaccine
A viral vector is another means of causing a safe immune response to a virus.
A viral vector works like a shuttle for transferring a gene that vaccine producers need. They take a gene from one virus, insert it into the genetic sequence of some other harmless genetically altered virus, and then use it in vaccine production.
The drawback of viral vector vaccines is that some might not work in people who are already immune to the virus from which the vector was made. For instance, the anti-COVID-19 viral vector vaccine is based on the primate adenovirus and might have little or no effect on those who already had a history of adenovirus infection.
Viral vector vaccines are also produced relatively quickly. They cause minor side effects—headache or fever—and are considered to be just as safe as DNA/RNA vaccines.
Subunit or ghost vaccine
Subunit vaccines can be made of any viral or bacterial particle to which the immune system can react. It can be a protein or even a part of a polysaccharide (a super-molecule composed of simple sugar molecules like glucose).
Why polysaccharides? They are usually found in bacterial capsules that defend bacteria from antibodies or harsh environments. These super-sugar molecules are typically characteristic of their owners, so our body can recognize an intruder by them. Some subunit vaccines contain complexes of polysaccharides and proteins. The latter make the transportation of the polysaccharide more efficient and provoke a more robust immune response because a human body usually responds to antigen proteins more rapidly and remembers them better than polysaccharides.
Subunit vaccines cause a less efficient immune response than the others, yet they are safer for patients with immunodeficiencies.
They are used to stop meningococcal, pneumococcal, and influenza infections.
How do they test vaccines?
Before a vaccine becomes available to the public, it has to be tested and approved. There are at least three phases of vaccine testing that sometimes can take years or even decades, as was the case with the Meningococcal B vaccine.
Basically, the phases differ by the number of the population involved in the trials:
Phase 1: up to 100 people
Phase 2: several hundreds of people
Phase 3: several thousands of people
During these clinical trials, scientists discover all the possible side effects.
A quality vaccine should contain not only a pathogen particle but also other chemicals that make it safe and stable:
- Preservatives prevent contamination by other microorganisms
- Stabilizers prevent undesirable chemical reactions that can damage pathogen particles
- Surfactants make molecules, and all the ingredients hold together.
Some vaccines also contain adjuvants that alter immune responses. All these chemicals have to be tested for safety and dosages, too.