What is the Immune System and How Do Vaccines Work?

By Kathleen Navas, Edited by Sami Morse

This blog attempts to create an engaging introduction to the basics of the immune system and a brief overview of the different types of vaccines being developed for COVID-19.



The Immune System:

Our immune systems are responsible for getting rid of dangerous infectious agents called pathogens. All living things more sophisticated than lobsters have two parts to their immune system: nonspecific and specific immunity.

The nonspecific (aka innate) immune system identifies disease by sensing danger/damage. When your body recognizes that a foreign organism (bacterial, viral, or parasitic) is damaging its cells, it sends in the PacMen of the immune system to get rid of that foreign danger. These cells, broadly categorized as phagocytes, are nonspecific because they’ll eat anything that your body labels as dangerous. A phagocyte can’t tell the difference between the flu and coronavirus, but it can identify them both as dangerous. Additionally, phagocytes signal to the specific immune system (the expert cells that can differentiate) to come take a look at whatever it has labelled as a danger.

The specific (aka adaptive) immune system is more intricate, but it forms the basis for vaccinology. The specific immune system creates cells called lymphocytes. Your body generates millions of different “clones” of lymphocytes. Each “clone” has a different cell surface receptor that gives the specific immune system its specificity. One receptor can only recognize one very specific protein on a pathogen. This arm of the immune system can differentiate between the flu and the coronavirus. When a lymphocyte’s receptor attaches to its pathogen, your body launches a whole host of specific responses: killing infected cells, creating antibodies that can clear pathogens from your bloodstream, and reinforcing the inflammation response.

Although lymphocyte clones are created randomly, every single person has one lymphocyte clone among millions that is vaguely better at recognizing SARS-CoV-2 than anything else. Having only one specific clone is not enough to be immune to a disease. Catching the disease encourages your body to fine-tune the receptor and expand the clonal population. This generates immunity against future infections. However, on a population scale, that comes at a giant cost when the disease in question is dangerous enough to kill thousands of people. The goal of a vaccine is to generate immunity (expand the specific lymphocyte clones to protect you against future SARS-CoV-2 infection) without the side effects and mortality rates of catching the disease.

Different Vaccine Types and How They Work:


1. Live attenuated vaccines:

The first modern vaccine, which eradicated smallpox from the world in the 1970s, was a live attenuated vaccine. The smallpox vaccine was invented before the scientific community even knew about the germ theory of disease. Live attenuated vaccines are exactly what they sound like: “live” versions of the disease that can replicate and invade cells and localize properly. They’re also “attenuated,” which means they’re weaker versions of the disease. They can be weakened artificially (nasal flu spray vaccine) or they can be slightly different diseases entirely (cowpox as a vaccine for smallpox).

Advantages: Mimicking natural infection causes stronger and longer lasting immunity. Disadvantages: Needs to be refrigerated, which can make it difficult to use in some places. People with immunodeficiency disorders often can’t take live attenuated vaccines because their immune systems are not strong enough to even fight off the more attenuated version of the disease.

COVID-19 Specific: There are no live attenuated versions of coronavirus being used in vaccines. However, similar to the way cowpox was used to vaccinate against smallpox, scientists are exploring the effectiveness of BCG - commonly used outside the US to vaccinate against tuberculosis. We’ll try to post blogs on each of these potential coronavirus vaccines this week, so stay tuned for more!


2. Inactivated vaccines:

Inactivated vaccines utilize heat, chemicals, or radiation to kill the pathogen without altering the antigen shape, thereby allowing an individual to develop long-lasting immunity to the pathogen’s proteins without possibility of infection.

Advantages: Fully safe regardless of immunodeficiency. Can be freeze dried and shipped anywhere easily.

Disadvantages: Lower efficacy. Your body expands lymphocyte clones on an as-needed basis. If it doesn’t recognize the vaccine as a dangerous invading pathogen, you won’t get full immunity without administering multiple “booster” shots.

COVID-19 Specific: The Chinese company Sinopharm has an inactivated virus vaccine in phase 3 trials. On September 14th, Sinopharm was approved for emergency use in healthcare workers in China only, despite some side effects. Also in China, Sinovac Biotech has CoronaVac in phase 3 trials and approved for limited use.


3. Protein based: If we know what proteins specifically we want to generate immunity against, scientists can grow the pathogen in the laboratory and then isolate those proteins to create a vaccine. Alternatively, we can artificially generate the protein itself using recombinant techniques. Only the protein of interest is introduced into the patient’s body.

Advantages: Like the inactivated vaccine, this reduces the likelihood of adverse side effects and makes the vaccine easier to ship.

Disadvantages: Your body may not recognize the protein as a threat, which can reduce effectiveness, also like with the inactivated vaccine. The less similar the vaccine is to the real infection, the more difficult it is to create an effective vaccine that generates long lasting, strong immunity.

COVID-19 Specific: You may have heard about coronavirus’ spike protein (if not, you can learn more about it here). Novavax (US company) is developing a vaccine using just the spike protein from SARS-CoV-2.


4. Recombinant vector vaccines

The goal of vaccination is to generate an immune response against specific coronavirus proteins without giving the patient COVID-19. One way to do that is to introduce the SARS-CoV-2 specific proteins using a different virus. In a lab, scientists can add selected genes from the pathogen to a less dangerous viral vector, thereby creating long term immunity to coronavirus proteins via a relatively harmless virus.

Advantages: The vector is a live replicating virus, which gives you the benefits of attenuated vaccines (a stronger, longer lasting immune response) without the danger. This strategy has been used with some efficacy in HIV vaccines and even Ebola vaccines. This strategy is most often used for dangerous diseases to lower risk of side effects.

Disadvantages: Efficacy may be lost if the individual was previously immunized with components of the viral vector. Depending on the vector, there may be potential for the generation of a pathogenic vector in vaccinated individuals.

COVID-19 Specific: CanSinoBio (Chinese), Gamaleya (Russian), Johnson & Johnson (US), and AstraZeneca (British-Swedish) all have recombinant COVID-19 vaccines using an adenovirus vector in phase 3 trials.


5. mRNA based vaccines

There are currently no mRNA based vaccines on the market. This is a new type of vaccine being developed specifically in response to the pandemic. If you’ve never heard of RNA, this is a type of genetic material. Inside your nucleus, your body holds DNA, which is your genetic code. This is turned into RNA, which can be read by proteins (ribosomes) to create more proteins.


Interestingly, some viruses encode their entire genomes in just RNA, which makes them more prone to mutation. SARS-CoV-2 is an RNA virus that relies upon your body’s ribosomes to create coronavirus surface proteins. An RNA based vaccine introduces the RNA that encodes the coronavirus into your cells, which then create the protein of interest themselves. This could theoretically be more effective than just a protein based vaccine because it mimics real illness more accurately. Some experts think that RNA vaccines have the potential to be safer and faster to create, so maybe we will see more of these in the future.

COVID-19 Specific: The two mRNA based coronavirus vaccines in Phase 3 clinical trials are Moderna and BioNTech.

Results from ongoing research and the current understanding of COVID-19 are constantly evolving. This post contains information that was last updated on October 21, 2020.

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