Why Do Vaccines Take So Long To Make?

A Peek Into the Vaccine Development Industry

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If you’re anything like me, you’re tired of being in lockdown because of the coronavirus, or SARS-CoV-2.

You’re tired of having to put on a mask every time you go to get groceries.

You’re tired of maintaining a 2-meter distance from everyone, acting like you are repulsed by everyone else.

You’re tired of being bombarded by bad news surrounding the outbreak, and the number of deaths it has caused.

The coronavirus outbreak is getting out of hand. Source: Bangkok Post

And we have all right to be tired of this. Many of us might have lost our jobs, or haven’t made a proper income for months at this point.

Now, there’s many ways this could’ve been prevented. Maybe if it had been handled well, in terms of federal regulations, etc., on part of the World Health Organization (WHO), or most countries around the world. Maybe if we had some way to predict exactly how bad this could get, or how it would spread around the world. Maybe people hadn’t been so ignorant and continued to gather in public despite the threat of a deadly pandemic.

But all of these things are behind us, or at least partially. We still need governments to handle the situations properly moving forward. We still need people to be responsible and avoid gatherings and unnecessary interactions. We still need the WHO to step in.

But what we need more than anything, is a vaccine. I mean, if all of us could be vaccinated tomorrow, and become completely safe from contracting the novel coronavirus, all our problems would be solved. We wouldn’t necessarily need to social distance after that, and we could all return to our normal lives. Which makes you wonder: why exactly is it taking soooo long to make a vaccine?

Side Note: To get a better idea of how the immune system works, and how vaccines might help, check out my friend Aaryan Harshith’s article on immunology:

Companies are Looking for a Profit

Let’s take a journey back to January 2020. China has just announced that it’s dealing with outbreaks of the coronavirus, and asserts that they have the virus under control (we all know how that turned out). At this point, there’s only a couple hundred reported cases, and none outside of China.

Now, imagine you were running a big pharma company, or a biotech startup at that moment. Would you invest millions of dollars into making a vaccine for the coronavirus at this point in January? Of course not! There’s barely any patients, and the country of origin says they’ve got it completely under control. Distributing a vaccine for such a disease wouldn’t lead to any profits whatsoever.

Over the next couple of weeks, the situation remained virtually unchanged. Cases had appeared outside of China, and were growing rapidly, but still not anywhere near a profitable level. And then, the outbreak really started taking off in countries like Italy, Spain, Iran, and the United States, and the situation was finally defined as a global pandemic.

And it is at this point that you might start instructing your researchers to look for a vaccine. Because, now, you can be sure that people are going to want vaccines, and that you can truly make a profit off of your vaccine research.

And this is the first big factor that adds to the amount of time it takes to make a vaccine after a disease appears. The process to develop a vaccine can cost millions of dollars, and no company is going to pursue it unless they can ensure they will make even more money.

But why does it cost so much in the first place?

Vaccine Checkpoints

Making a successful vaccine is a long process, requiring researchers to pass through a certain number of regulations, or checkpoints, before being able to move onto the next step.

Step #1: Exploration

The first of these steps is the exploration phase. This is the phase where researchers try to find as many possible molecular candidates that might be able to target the given pathogen.

This phase starts with identifying the type of virus, and determining some defining characteristics for the virus. In the case of SARS-CoV-2, the virus itself is an RNA virus (meaning that it carries RNA as genetic code instead of DNA). These viruses are the hardest to deal with, since RNA replication does not have any error-checking mechanisms, meaning that the viral genetic code can easily mutate, allowing the virus to constantly evolve. This specific virus also belongs to the viral family coronavirus (yeah, that’s the name of a group of viruses, not the virus itself), which contain other notable members like the SARS virus that caused an outbreak from 2002–2004, and the MERS virus in the Middle East. Knowing what family the SARS-CoV-2 virus belongs to gives us another major characteristic: the spike proteins present on all coronaviruses (which give the virus a crown-like appearance).

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The spike proteins give the coronavirus their characteristic appearance. Source: National Institutes of Health (NIH)

These spike proteins are crucial for the virus, since they interact with some proteins on the surface of their target cells, allowing them to enter and infect the cell in the first place.

Another crucial piece of information that researchers try to find early on is the genome of the pathogen. This allows them to understand the structure of the virus at a deeper level, and lets them find out the rate at which different parts of the genome mutate/evolve, allowing them to find protein targets based on genes that change very little (so that the vaccine can be generalized without the risk of the gene being targeted rapidly evolving).

After they have all of this information, researchers can finally start looking for natural or synthetic antigens that might treat or prevent the disease. These antigens could be virus-like particles, weakened viruses or bacteria, weakened bacterial toxins, or other characteristic substances derived from the pathogens.

Step #2: Pre-Clinical Trials

Once researchers identify a host of different antigens that might be effective, they enter pre-clinical trials, which involve experiments on tissue-cultures and animals (ex. lab mice). The researchers are basically trying to determine if the candidate will produce immunity and whether or not it will produce harmful effects. Most candidates actually don’t make it past this stage because they either fail to produce immunity, or because they cause harmful side effects.

But how exactly would a vaccine “produce” immunity? Well, producing immunity in this case talks about whether or not a specific antigen will cause the body, or the immune system specifically, to react and attack the pathogen. If the body recognizes something meant to generate immunity against the coronavirus, for example, than that’s good. But just the fact that the body reacts is not enough.

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Phagocytes, one type of immune cell, protect the body from invaders by literally eating them up, and then dissolving them alive with enzymes inside itself

Having a successful vaccine requires the body to also remember that pathogen. I meant that’s the entire point of a vaccine. Introduce some defining feature of a disease to the body, and train the body to recognize and attack it, so that if it is infected with the actual disease, it can immediately fight it. And so, researchers also have to test if the tissue cultures and animal experiments are able to produce a similar immune reaction after the vaccine is administered.

And at the same time, researchers have to test for how strong a reaction the body produces, since in some cases, antigens can cause severe inflammation in the body (which we obviously want to prevent).

If a candidate successfully passes each of these tests, it can finally move on to the next step in the process.

Step #3: Clinical Development and Trials

And now we finally get to testing the vaccine candidates on humans. To get this process started, the researchers/company working on the vaccine candidate first has to submit an application for an Investigational New Drug (IND) to the FDA (U.S. Food and Drug Administration). Once this has been approved (after checking over a long and kind of boring list), the vaccine trials can finally begin.

The first phase of vaccine trials involves only a small group of adults (less than 100 people) just to determine whether or not the particular vaccine is safe to administer or not, and the type and extent of immune response the vaccine provokes. And in a very small number of subjects, researchers might also attempt infection with the actual pathogen to observe how the body reacts to it post-vaccination. Unless the vaccine candidate delivers promising results for all of these tests, it will not move past phase 1 of trials.

Phase 2 involves testing with a larger group of hundreds of individuals, some of which might be particularly at risk of acquiring the disease (like seniors in the case of COVID-19). The goals of these clinical trials are to further study the vaccine candidate’s safety and ability to create an immune response, and determine optimal doses, immunization schedules (not necessarily for all pathogens), and the best method of delivery.

Phase 3 involves testing tens of thousands of people, and involves the experimental vaccine candidate to be tested against a placebo drug (could be a saline solution, a vaccine for another disease, or some other substance). One of the goals of this phase is to determine vaccine safety in a large group of people, in order to find rare side-effects to the vaccine (ex. some side effects might appear in only 1 out of thousands of people). These trials also test for vaccine efficacy, looking at factors including:

  1. Does the candidate vaccine prevent the disease?
  2. Does it prevent infection with the pathogen?
  3. Does it lead to production of antibodies or other types of immune responses related to the pathogen?

And if everything goes as planned in this last phase, the vaccine has been found. After this, the FDA just needs to grant a license to the company behind the vaccine, after which they can begin widespread production.

Speeding It Up

So, that’s a lot of steps for just one vaccine. But they’re all super necessary, to make sure that the vaccine is super effective and extremely safe to use (wouldn’t want to give any more fuel to the anti-vaccination community now, would we). But as simple as all of these steps sound, they can take years to carry out. Most of the vaccines we have made up to now needed about 10–15 years to make. The record for developing a completely new vaccine is at least four years.

There are, however, several ways this can be sped up, all of which are currently being researched. The most exciting of these is the use of artificial intelligence (AI) in several phases of vaccine development.

In the exploratory phase, AI can be used to process vast libraries of data, like analyzing properties of thousands of pharmaceutical compounds, with more accuracy, to arrive at potential candidates. In the pre-clinical stage, AI can also be used for DNA sequencing for patients, to determine specific genetic factors responsible for different reactions.

Overall, the vaccine development industry is prime for innovation, which is critically needed to ensure that pandemics like the coronavirus pandemic going on right now can be prevented in the future.

On A More Personal Note:
I am a
17-year old currently obsessed with the science behind aging, and if we could live forever (because, let’s be honest, no one wants to die).
I do have more articles coming up on the
coronavirus vaccine research right now, and on cancer stem cells (super excited for this one), so if you want to read more of my articles, follow me here on Medium. And check out some of the other articles I have written, on various topics from AI, to gene editing, to life and philosophy.
To find out more about me and what I’m working on, check out my
website, and my Twitter.

That’s all for me now. See you next time!

Written by

17 y/o innovator working on reversing ageing and researching cancer. www.akshajdarbar.com

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