All You Ever Wanted to Know About COVID-19 Vaccine Candidates

Why is a coronavirus vaccine taking so long? And which country is prepping the fastest?

There’s a global race to find a cure for the coronavirus that has put the world on lockdown. Currently, 180 vaccines are in several stages of clinical research according to the World Health Organization, and experts estimate it could take anywhere from 12-18 months to get results.

Recently, the Oxford vaccine resumed their clinical trials in the UK following confirmation by the Medicines Health Regulatory Authority (MHRA) that it was safe to do so. On 6 September, the standard review process had triggered a voluntary pause to vaccination across all global trials to allow review of safety data by independent committees and international regulators

On the Indian front, Hyderabad-based pharmaceutical company Bharat Biotech’s indigenous COVID-19 vaccine candidate Covaxin showed protective efficacy in animal trials. Meanwhile, phase 2 of Covaxin’s human trials have been kickstarted in Nagpur.

Globally, 35 vaccines are in the human trials phase. Although recently, Adar Poonawalla, CEO of Serum Institute of India (SII), predicted that there won’t be enough COVID-19 vaccines for everyone in the world till the end of 2024.

Why is it taking so long to create a vaccine? How do they work, really? And which vaccine are experts betting on? FIT explains.

First, here’s a quick primer on what COVID does to our bodies and why we even need a vaccine in the first place. Once the virus attacks, it infects our cells and uses them to replicate and spread throughout our body. It is a respiratory infection so the lungs are hurt the most, but most of the symptoms are a response to our immune system fighting back - often it fights too hard and causes a ‘cytokine storm’ which further damages our organs.

All of this can potentially be avoided if we are issued a vaccine before the virus strikes, so the search for a safe and effective vaccine is crucial to eventually end the pandemic, or at least acquire the much spoken about herd immunity.

What is a Vaccine?

A vaccine works by training healthy cells to recognize and counter a pathogen (a virus or bacteria). This is done by introducing a tiny amount of the pathogen, which then triggers or provokes an immune response by the body, thereby ‘training’ it to defend itself against the pathogen.

Anitbodies for Antigens

PublicHealth further explains that tiny molecules from the pathogen, which are called antigens, are introduced in a safe way to prepare the body. Our body learns to recognise these antigens as hostile invaders and produces protective antibodies to defend itself.

The idea is that when the virus attacks us in the future, our body will recognise them and have its defence strategy ready.

Why is it Taking So Long to Create a Vaccine?

Simply put, because it a complex process with several steps. We don’t want any vaccine that hasn't undergone the requisite testing and rigorous process to be ready for use. The process to design a vaccine and ensure it is safe for human use, takes anywhere between 10 to 15 years. But with the world’s focus on COVID-19, governments have fast-tracked applications and regulations to get out a vaccine in the super-short timeline of 18 months.

Step 1: Find the pathogen and extract the antigens. In January 2020, scientists in China published the genetic sequence of the novel coronavirus and made it easier for researchers worldwide to understand the virus better.

Step 2: Identifying vaccine candidates. Researchers do background knowledge on this vaccine candidate, also known as the live virus to determine the best way it can be used to provoke immunity in people. Often the genetic sequence of the virus, and not the virus itself, is used.

Step 3: Pre-clinical testing: Testing on animals to give researchers an estimate of how the vaccine would work on humans. They can then tweak the vaccine accordingly.

Step 4: Clinical trials: This is when testing on humans begins. Typically these occur in three phases:

• Phase I: Safety trials: Tests on a small, healthy sample to check the safety and adjust the size of the doses. This stage takes around 3-6 months.
• Phase II: Expanded trials: Increase the sample size to hundreds of people to test for efficacy on a target population who is more prone to the virus. This usually means the methodology is done on a randomised sample, with a placebo group as well. This phase takes around 2-4 years.
• Phase III: Efficacy trials: Further increase the sample size to thousands of people to test against various changes in populations. This stage takes around 2-4 years. For COVID-19, many vaccines are doing phase II and III together.

Step 5: Regulatory Review: A government regulatory body has to approve the vaccine and see if it is safe enough for mass production. This process in itself often takes 1-2 years but with the world’s eyes on COVID, fast-track responses are in place to expedite the regulatory and licensing process.

Step 6: Production. Significant manufacturing capacities like the exact machinery, labs, personnel and equipment will be needed for large-scale production. Quality control will be essential.

So in total, the entire process can easily take 6-12 years in general but will be expedited for a COVID-19 vaccine.

Types of COVID-19 Vaccine Candidates

Now vaccines are not a homogenous block and there are many different ways to develop an effective vaccine for the vast number of diseases we face. There are many types of vaccines: attenuated (live) vaccines, inactivated vaccines, toxoid vaccines, subunit vaccines, and conjugate vaccines.

But here is a list of all the types of vaccine candidates currently in the works for COVID-19:

1. Whole-Virus Vaccines

These types of vaccines use a weakened or inactive version of the COVID-19 virus to induce an immune response.

An inactivated vaccine or a killed vaccine uses the killed version of the pathogen that causes the disease. They are made from viruses or bacteria that have been killed clinically and therefore they cannot cause diseases anymore, according to WHO.

Inactivated whole-cell vaccines often cannot produce an immune response or if they do, the response will be short-lived. You may need many doses of the inactivated vaccine to provoke a sufficient response. Comparatively, vaccines made from live viruses are often more powerful at provoking immunity.

On the plus side, since they are inactive, they pose no danger of disease and are safe and stable.

Bharat Biotech’s new vaccine candidate, Covaxin, is a inactivated whole-virus vaccine.

2. Viral Vector

These vaccines use a virus to transfer the genes from COVID-19 into healthy cells to provoke an immune response.

Oxford University’s much-touted vaccine falls into this category.

3. Genetic Vaccines

This kind of vaccines uses one or more of the coronavirus' own genes to induce an immune response.

They are also called DNA vaccines as it involves the direct injection of genetic material into a living host to produce an immune response. This is done by creating an ‘inappropriate’ gene expression and so creates an immunological response which causes a specific immune activation of the host in response to that specific gene with the antigen.

4. Protein-Based

This vaccine uses a weakened or inactivated version of the COVID-19 virus to induce an immune response.

As of now, the most advanced vaccines candidates of this type are all being worked on in China.

5. Repurposed

These are vaccines that already manufactured and in use for other diseases, and could protect against COVID-19. Since these are already in existence, they ofter a more rapid hope for beating COVID, rather than creating and manufacturing a whole new vaccine.

For example, Remdesevir, the drug originally made for Ebola, was offered as a COVID-19 drug. Now while clinical results are inconclusive and not as promising so far, it is being tried out as part of a treatment plan for hospitalised COVID patients.

Profile of Vaccine Developers

So far, most of the vaccines are being developed in North America and then in Asia, particularly, China, and then Europe. There are several reasons for this including advanced infrastructure and existing development routes like research bodies, grants, etc.

There is not much public knowledge on efforts in South America or Africa, even though these countries do have the required infrastructure. It could also be that since no vaccine in the world is ready, efforts are kept hidden till a result is sure.

In general, the global outlook towards COVID-19 is unprecedented, and experts believe concerted efforts across the globe will lead to a fast-track, safe, effective vaccine. Usually the process takes around 6-12 years, with an average of 10 years to develop a vaccine. During the Ebola outbreak, the accelerated time-scale was still 5 years - but we are in a pandemic, and times are a-changing fast.

(The article was first published on FIT.)