The number of times a day that you encounter the word ‘vaccine’ has probably gone up a lot in the last five months. There is a barrage of news articles, viral videos and unverifiable claims from our family Whatsapp groups coming our way each day. In this moment, understanding how vaccines work and getting rid of misconceptions has a huge impact on our personal lives but can be frustratingly difficult. What are the differences between all the Covid-19 vaccines out there? Why does the Pfizer vaccine have to be stored at -70 degrees Celsius? Is it true that Covaxin can give you Covid? What are vaccines, anyway? This article explains how the immune system actually works, how vaccines confer immunity and why the new mRNA vaccine technology is important.
The Immune System is a Mad Genius
High school biology tells us of this supernatural-sounding, sophisticated defense mechanism residing in the body of each human being –– the immune system. Indeed, your immune system can fight against millions of pathogenic microorganisms that you constantly come in contact with. But how does it accomplish this feat? The immune system has two crucial abilities that protect you from diseases. First, it can recognize substances that are unwelcome in your body: pathogens such as bacteria and viruses. This is more complicated than it sounds, because our bodies are made up of cells that are similar in many respects to bacteria and viruses, and there are no well-defined rules that neatly separate healthy cells from pathogens. Second, the immune system can use biological pathways to destroy the recognized pathogens. The immune system can also recognize toxins such as dust particles –– the reason we sneeze and have a runny nose if it’s dusty or polluted. However, in this article we will focus on the interaction between the immune system and biological pathogens.
The first function of the immune system is like a text editor that recognizes incorrect grammar. We’ve all been caught red-handed while typing grammatically incorrect sentences in MS Word (quite literally –– MS Word informs us of this with a frustrating squiggly red underline). MS Word does this by using pre-defined grammar rules and checking whether sentences satisfy these rules. Now consider this. If the text editor in question operated like the immune system, it would literally construct every possible grammatically incorrect sentence, and then check each new sentence it encountered against this enormous library of incorrect sentences. Well, naturally, this system is much less efficient than verifying a few grammar rules. But remember, there aren’t any analogous rules that the immune system can use to distinguish pathogens from healthy tissue. So, it does what it can…
Right now, floating around in your body, are approximately one trillion immune cells, each sporting a unique ‘antibody’ (for context, the human body has roughly 30 trillion cells). These antibodies are made of small bits of protein, combined in arbitrary ways (the way our inefficient text editor would make up wrong sentences by combining random words). Each of these antibodies ‘fits’ a particular molecule that your body might encounter on a pathogen. If that pathogen molecule happens to enter your body and encounter the corresponding antibody, the antibody will lock into place and trigger an immune system cascade that will either neutralize (i.e., make unable to function) or destroy the pathogen. If you’re paying attention, you would have guessed by now that everyone in the world is currently walking around with a Covid-19 antibody in their system.
The natural question that follows is, why does anybody ever get sick? The answer is that it’s a numbers game. The likelihood that a single pathogen molecule will come into contact with its matching antibody in your body is very, very low. This likelihood gets higher as the pathogen replicates and produces copies of itself. Once the antibody-pathogen match occurs, your immune system starts producing many more of that particular antibody and starts destroying the pathogen copies. From there, it’s a race to see which group of cells (the pathogen or the antibody-containing immune cell) can replicate faster and conquer the other.
Vaccines: Leveraging the Fantastic Memory of the Mad Genius
Once your immune system has recognized a pathogen and raised antibodies against it, it does something amazing –– it memorizes the pathogen by always keeping a bunch of the relevant antibodies handy. So the next time you encounter that pathogen, the likelihood of it matching up with its antibody is much higher, the process of triggering the destructive immune system cascade is much faster and you are much less likely to fall sick. This is where vaccines come in. Vaccines are modified pathogens that don’t cause disease but are still recognized by the immune system as a foreign object. When the vaccine is injected into the body, the immune system generates and maintains an army of the relevant antibody; when the real pathogen shows up, these antibodies fight for you and you are immune to the disease. The commonly held notion that vaccines ‘trick’ the immune system into raising antibodies is subtly incorrect. The immune system is functioning as intended when it produces antibodies against a vaccine, but it’s simply getting a leg up because the vaccine can’t actually cause the disease.
How does one modify a virus to make a vaccine? The most commonly used and well-established technique is to inactivate it by heating it or exposing it to chemicals that denature the proteins that make up the virus (similar to what happens when you boil an egg). Covaxin, produced by Bharat Biotech, is an example of a whole-virion inactivated virus. Another common method is to take a different virus that is harmless to humans, and genetically modify it to produce a few proteins from the virus you want to vaccinate against. The harmless virus, when injected into the body, replicates and produces many copies of the proteins that were introduced into its genome. The immune system raises antibodies against these proteins that confer immunity against the harmful virus. Examples of such ‘viral vector’ vaccines are the Oxford-AstraZeneca Covid-19 vaccine and the Johnson & Johnson Covid-19 vaccine. The advantage of viral-vector vaccines over inactivated virus vaccines is that there is no chance of the vaccinated person contracting the disease due to incorrect inactivation of the virus.
The Covid-19 pandemic has fueled advances in a new type of vaccine that does not require a virus at all. You may remember from high school biology that proteins are made from mRNA, which is made from DNA (the genetic code in your body’s cells). These non-viral vaccine delivery systems make use of DNA or mRNA fragments that encode proteins from the virus that you want to vaccinate against. The DNA or mRNA fragments are packaged in such a way that makes them appear non-foreign (basically, they are coated with the same oily molecules – lipids – that form the surface of our healthy cells). When the lipid-coated genetic material is injected into the body, it is taken up by immune cells which use it to produce the virus’ proteins. In this case, you actually are tricking the immune system into doing something it ordinarily isn’t supposed to. Once there are enough of the virus’ proteins floating around, the normal function of the immune system kicks in and it starts making antibodies against the virus.
Both the Pfizer and Moderna vaccines are mRNA vaccines. Their advantages are that they are more amenable to quality control and can be designed and manufactured in a short time scale. However, mRNA is much more chemically unstable than protein or whole virus, and so it needs to be stored at much lower temperatures. Another disadvantage is that since these mRNA vaccines have not been around for long, there is no data on potential long-term side effects.
There are currently 12 different Covid-19 vaccines that have been approved, with loads more in the pipeline. As we race to get enough people vaccinated in time to achieve herd immunity, it is vital that we all participate in the effort by getting vaccinated ourselves and encouraging our close friends and family to do the same. I hope this article will help you navigate the debates and discussions with more confidence.
Amrita Singh has a B. Tech in Biological Sciences and Bio-Engineering. She is currently pursuing a PhD in neuroscience at Janelia Research Campus in Virginia, USA.
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