Everything you need to know about the Coronavirus Vaccine

From how it works to the opportunities and challenges it presents

Ever since the pandemic hit and all of our lives were confined to the limits of our homes, the one question that has been on everyone’s mind is: How long will the COVID19 vaccine take?

Which Vaccine is the right one? I got expert advice from a friend who has nothing to do with healthcare, “You should wait until x million people have taken it!”, “The Vaccine may have long term side effects”, et el.

I’ve been thinking about traveling and yes, I’m tired! Not of covid but random advice from all our friends. So I decided to do a deep-dive & make life simple for y’all.

Pro tip: Don’t miss reading about mRNA ;)

As I write, the ongoing pandemic has infected over 76 million people and claimed the lives of more than 1.6 million people, and the race to develop an effective and safe vaccine is on.

Almost a century ago, the Spanish flu of 1918, amongst the deadliest epidemics of all time took over 50 million lives and it wasn’t until 1945 that the first vaccine was approved for usage. 

Truth be told, vaccines take years and more often decades to be developed, read how long it took for other common vaccines here. Thanks to the biotech companies and scientists across the globe working at lightning speed, we finally have some good news as the year comes to an end with a handful of vaccines approved for usage.

Fast-tracking the process to develop a vaccine in 12-18 months is a record never achieved before. Given that these aren’t normal times, the only option was to keep trying and hope that we get lucky. This brilliant New York Times piece that came out in April’20 highlighted how this impossible task could be achieved and we see that beginning to bear fruit now.

As per this tracker, currently, there are 63 vaccines in clinical trials on humans out of which 2 vaccines have been approved for full use. In this issue, I’ll touch upon the vaccination technology, how they work, what’s new with the approved vaccines and the opportunities and challenges that they present.

Outline:

→ History of Vaccination

→ Vaccine Development >> Types of Vaccines | Trial Stages

→ mRNA: The Disruptor >> A Scientist’s Unwavering Determination | How it works?

→ Opportunities for Tech Firms

→Challenges and the path ahead

History of Vaccination

The words vaccination and immunization are often used interchangeably, and the practice of immunizing against an infection dates back to hundreds of years ago. The idea is simple, vaccines train your immune system to recognize and fight off the virus/bacteria targeted, so that later when your body gets exposed to the germ, it is ready to fight and prevent any illness.

The Origins

One of the deadliest diseases to have ever existed on this planet was Smallpox killing millions across all regions. The story of vaccination also starts here, the early attempts included scratching smallpox scabs into a recipient’s skin (inoculation) to provide immunity against the disease. The method, however, wasn’t entirely successful and was met with opposition when further outbreaks were triggered.

It was only in the second half of the 18th century that the English physician Edward Jenner noted that dairy farmers did not contract smallpox. Connecting the dots, Jenner realized that the mild illness of cowpox can be used for immunization against smallpox.

After a series of experiments, Jenner inoculated a teenage boy with the cowpox virus to demonstrate protection against smallpox in 1796. Later, when the boy was exposed to smallpox several times, he did not develop an infection. 

Jenner tried this on several other patients and established that once the immune system is exposed to the cowpox virus, it is ready to take on smallpox. Thus, the first vaccine was created, finding its root in the Latin word for cow - Vacca! Thanks to Jenner, now regarded as the father of immunology and vaccination, thousands and thousands of lives could be saved and smallpox was eradicated from the face of our planet in 1979.

The expansion

Apart from Jenner, the French biologist Louis Pasteur (who we need to thank for our daily dose of ‘pasteurized’ milk) made immense contributions to the field of vaccination. Starting from experimentation on chickens to prevent chicken cholera using a weakened form of the disease of provide immunity and a vaccine for Anthrax in 1885 to saving the life of a nine year old boy badly bit by rabid dogs, Pasteur demonstrated that one can get rid of all these diseases by vaccination.

Pasteur’s success made him an international hero and his treatments were henceforth called Pasteur’s process. However, as a tribute to Jenner’s influence on him, Pasteur decided to use the term vaccine for all sorts of treatment including live, weakened, or attenuated microorganisms to induce immunity against a disease. 

Pasteur’s story and how he came up with his treatments deserves an article of its own and if you are interested, you can check this out. Building upon the work of Pasteur and scientific advances in the first half of the 20th century, vaccines were developed against a number of deadly diseases such as whooping cough, tuberculosis, diphtheria, tetanus, influenza, mumps, measles.

Jonas Salk developed the first successful vaccine for Polio around 1955 and as of today, apart from three countries (Pakistan, Nigeria, Afghanistan), all the other countries have been successful in eradicating polio. Vaccine production also scaled up in the mid 20th century and with a series of public health campaigns, vaccination rates shot up everywhere. Children's deaths were halved and vaccination has proved to be the success story of centuries.

Vaccine Development: How does it work?

By now you know that to develop immunity against a disease, we need some sort of exposure to disease-causing agents. In this section, we’ll take a look at the types of vaccines that are currently under development and trial process.

Types of the vaccine under development

Following this paper by van Riel and de Wit, the COVID vaccines under development can be categorized as classical, the vast majority of vaccines currently licensed for human use and proven to be highly successful as mentioned above, and Next-Gen based on the sequence information of the virus to develop the vaccine instead of culturing the virus.

Classical Platforms

Whole Inactivated: These vaccines use the killed germs that cause the disease i.e. a germ that is completely inactivated. The immunity provided by them is not that strong so you need to get several doses/booster shots over a period of time.

Live Attenuated: These vaccines use a weakened/attenuated form of the disease-causing germ. They are very similar to natural infection and thus create a strong immune response and a couple of doses are sufficient to provide lifelong immunity. Since they contain weakened live viruses, they are not recommended for everyone and depend on a person’s health condition. They also need to be kept at low temperatures and required refrigeration, so their storage can create problems.

Subunit/Conjugate: These vaccines use a part of the disease-causing germ, for example, its protein or sugar. Since they contain only a subunit of the germ, they provide a strong immune response against this targeted part. They can be used on everyone, however, they too require multiple booster shots to provide ongoing protection.

Next-generation Platforms

Viral Vector: These vaccines contain viruses that are engineered to carry the genes of the disease-causing viruses. These vectors (virus carrying the genes) can either be replicating or non replicating. The nonreplicating ones enter the cells and cause them to make viral proteins/antigens whereas the replicating ones create copies of themselves carrying the proteins to different cells. Both of these methods provide a strong response and a single dose is sufficient.

Genetic/Nucleic Acid-based: These vaccines contain the genes of the disease-causing virus to generate an immune response. They can consist of DNA or mRNA and can be adapted very quickly, that’s why they are among the first to enter the trials (more on this in the next section).

Testing/Trial stages of vaccine development

You must have read over the past few months that so and so vaccines are entering particular stages, here’s what these stages of vaccine development mean

1. Preclinical Testing: The vaccine is first used on animals such as mice to see if provokes an immune response

2. Phase I Safety Trials: The vaccine is given to a small number of people (20 -80) to test its safety and dosage, as well as to see if it produces an immune response in humans.

3.Phase II Expanded Trials: The vaccine is given to hundreds of people (100-300) split into groups, for example on the basis of age to see if the vaccine affects them differently. 

4. Phase III Efficacy Trials: In the next phase, the vaccine is given to thousands of people (1000-3000) and scientists wait to see how many get infected and compare it to people who have just been given a placebo. These trials determine the success of the vaccines measured in terms of the efficacy rate which is basically the ratio of people infected in two groups (placebo and vaccinated). Since these trials are large, they also reveal potential side effects.

5. Approval: The final stage where authorities/regulators review the results and of trials and determine whether it should be approved for human use and further plan for manufacturing and distribution.

To fast track the COVID19 vaccine development process as mentioned earlier, the scientists are using combined phases i.e. combining two stages together to go on simultaneously, for example Phase I/II trials. Also, a few countries like Britain have given early/limited authorization for the vaccine on the basis of preliminary evidence whereas China and Russia have authorized vaccines for use while their phase III is still ongoing which has made vaccine experts worry. 

mRNA: The Disruptor

Leading the vaccine developments race are New York-based Pfizer working with German comping BioNTech, and Moderan, a Massachusetts based vaccine developer. Both of them announced that their vaccine had an efficacy rate of 95% last month and their vaccines have been approved for early/limited/emergency usage in the US. And if you look at the table below, these are the only two developers to use mRNA.

A next-gen vaccination platform, mRNA or Messenger Ribonucleic Acid is genetic information that our cells read to make proteins. In COVID’s case, mRNA will prompt the cells to make a SARS-CoV-2 spike protein and thus train the immune system in recognizing the virus. 

A Scientist’s Unwavering Determination

The essence of this write-up, mRNA is the disruptive tech in the vaccination industry that has captured everyone’s attention. Though it is relatively new to the scene than other classical platforms mentioned above, the tech has been there since 1990. Its prospects have always been quite promising ever since it was developed to treat cancer, but it kept hitting roadblocks. 

Katalin Karikó, as a PhD student chemically synthesizing RNA in 1980 while working in the RNA laboratory of Biological Research Center of the Hungarian Academy of Sciences

I’d suggest the readers read this Stat piece that talks about the story of mRNA and how Katalin Karikó, the scientist behind its discovery, never gave up despite facing multiple rejections for decades before it turned into a multi-billion dollar technology. 

As Telegraph reports: “For more than four decades, Prof Karikó has relentlessly explored how the single-stranded molecules of genetic code could be used to treat conditions from strokes and cancer to influenza. Despite demotions, countless grant rejections, and, at points, deep skepticism from fellow scientists, she ploughed on.” 

If it wasn’t for Karikó’s determination and strong will power, the world wouldn’t be on the brink of this key breakthrough to tackle the menace of our lives that is COVID. mRNA-based vaccines have developed earlier for several viruses such as influenza, HIV, Zika, rabies, etc. but the process sped up due to corona, and rightly so. The key advantage of mRNA vaccines is they are much faster to develop and manufacture compared to the classical methods, which was indeed the need of the hour too fast-track the process.

How does it work?

Step 1: Coronavirus uses its spikes produced by the spike proteins inside it to enter a human cell. Scientists synthetically create the genetic sequence (mRNA) that our cells can read for building the spike protein.

Step 2: The mRNA molecules are fragile and can be destroyed by the natural enzymes present in our body if they are injected directly, so they are wrapped in an oily bubble made of lipid nanoparticles. This bubble containing mRNA (vaccine particle) is then injected into the human body.

Step 3: The vaccine particle upon getting injected bumps into the human cell and fuses with it to release mRNA into the cell. The cell’s internal machinery then reads this sequence and starts producing the spike protein and the mRNA from the vaccine is eventually destroyed in this process. The spike proteins produced form spikes on the cell’s surface, some of this protein is broken into fragments and that too makes it to the surface.

Step 4: When the vaccinated cell dies, it releases debris of protein fragments and spike proteins that is detected by the immune system to trigger a response.

A detailed step by step illustration can be found here.

Opportunities for IT/Tech Firms

The corona vaccine distribution opens doors to multiple opportunities for tech and IT firms. The tech companies can venture into the business area of pharma companies as the world prepares for a vaccination drive for billions. 

IT majors have already started working on this. Infosys launched a vaccine management system last month based on Salesforce while Genpact has partnered with the UK government on reporting adverse reactions to the vaccine. Accenture too announced a comprehensive vaccine management solution for government and healthcare organizations to effectively plan and develop COVID-19 vaccination programs. 

Given how everything is fast-tracked, the governments would want this rollout to be as smooth as possible and have already started allocating funds for analytics-based solutions for patient management i.e. scheduling appointments, monitoring the doses and side effects, what segment should get preference, contact tracing, etc.

Secondly, the supply chain and logistics need to be worked out. I talked about IoT in the previous issue on the future of telecom, they’ll play a huge role in monitoring the distribution chain. Further, the vaccines need to be stored at cold temperatures, for example, Pfizer’s vaccine needs to be stored at -70 degree celsius whereas Moderna’s requires -20 degrees celsius. Hence, they have to be monitored for quick distribution and spoilage.

All of this presents a huge responsibility for IT firms that can now provide distribution and logistics solutions in addition to their software services leveraging their experience. We will see the importance of their role in the days to come.

Challenges and the Path Ahead

Despite the good news, there are a series of challenges that the world will have to face in the coming months related to accessibility and distribution of the vaccine as well as winning the public’s confidence. 

The accessibility issues have always been there with vaccines, the richer countries are able to guarantee access to its citizens while developing countries struggle to do so. For instance, the US and Canada have already signed unilateral deals with different manufacturers. Take a look at this chart below showcasing countries that have secured vaccine access:

Though there’s a need for a collective approach towards the vaccine, governments would rush to prioritize their own populations for easing their lockdown restrictions and reviving the economy. At the start of this century, Bill and Melinda Gates Foundation along with its partners set up the Global Alliance for Vaccines and Immunization (GAVI) encouraging manufacturers to lower their vaccine prices for developing countries. WHO has been working in conjunction with GAVI to provide equal accessibility to all.

The second challenge is that of trust, making people believe that the vaccine is safe and effective. Vaccine hesitancy or anti-vax is nothing new, there are anti-vaxxers all over the world refusing to accept any form of vaccination. From the beginning of the pandemic breakout, there have been a lot of conspiracy theories going around and how all of it is a scam. Tackling this sort of misinformation has been a huge challenge for governments worldwide. 

The rushed vaccination process is also adding to the vaccine hesitancy of people. Winning people’s confidence is not going to be easy, however, it is possible via transparency and communicating the right message.

How all of this unfolds in the next few months would be an interesting space to look out for, though it’s not like that we have a choice here. If you got value from this, feel free to share it with your network. :)