When will vaccine against COVID come? Understanding the process and timelines

Major update: October 03, 2020

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The race to develop and then mass-produce a vaccine against SARS-CoV-2, the virus behind the coronavirus pandemic is on throughout the world. A large number of private and government companies and labs are working overtime to create what is being seen as the ultimate protection against the disease.

As on 3rd October, 193 different vaccines are under development, in various stages. In normal course, each of them would have taken years to become a vaccine that can be administered to humans. However, many factors have contributed to the squeezing of time taken, in the case of COVID vaccines, mainly the following:

• The urgency for developing  a vaccine before it is too late has made all authorities and the WHO to modify guidelines and give permissions fast.
• There is global collaboration in vaccine development like never seen before.
• Human challenge trials: Volunteers are being enrolled so that they are administered vaccine and then infected with actual virus. Though there is controversy regarding its ethicality, such trials are being permitted to compress the time taken in trials; in natural course, infection in sufficient number can take years.
• Simultaneous trials: Vaccine development passes through many Phases. Without waiting for a previous Phase to complete, trials are allowed for the next Phase so that more than one Phase of trials is completed simultaneously.
• Availability of some vaccines in different stages of development for other coronaviruses.
• A better understanding of the human genome and that of the virus has made it possible to take the shorter route of using RNA sequences for developing vaccines.
• Not waiting for additional substances to be added to vaccine to make it more effective (which was traditionally being done earlier). Thus the developers keep focus on the primary substance and do not spend time on other substances.
• Some companies have already started large-scale production of doses of vaccines under test, so that when they pass the final stage, there will already be millions of doses ready. (That is a financial risk, but some companies are ready to take that, hoping to harness the first-mover advantage in case the vaccine succeeds.)

What are the different routes being taken by labs in developing vaccines against COVID-19?

In very simple terms, vaccines are biological substances that, when administered to people, activate their immune system to prepare it against a pathogen. 

 

What happens is that specialized cells/ molecules in human body react to the external substance (vaccine) and prepare the body to ward off a similar substance (when actual infection occurs). Some cells or their parts also have the capacity to remember the substance long after the vaccine was administered.

Any substance that can trigger a defensive reaction from the human body is a potential vaccine candidate. In the case of COVID-19, the following are the main types that fit the bill:

1. Genes from coronavirus: Pieces of the virus genome, when entered into human body in the form of vaccine, trigger reaction from its immune system.
2. Full but weakened virus: The vaccine can have a weakened form of virus, which forces human body to produce antibodies (and take other related protective measures) against it. But since the virus is not strong enough, the vaccine does not cause the disease.
3. Proteins from the virus: Human body reacts to alien proteins. (We get allergies usually due to such a reaction.) The virus uses different types of proteins to attack cells or tiny organelles within cells. So, if such proteins are introduced into human body through a vaccine, the body prepares itself against actual attack by the virus.
4. A different virus to deliver coronavirus genes: A virus that is not harmful to humans can be used as carrier of coronavirus genes.
5. In addition, a vaccine that is effective against another similar virus can, sometimes, protect against coronavirus.

What are Phases of trials in the development of a vaccine?

A 'vaccine candidate' or vaccine under development has to pass through at least 5 stages before it gets final approval for human use.

Pre-clinical Testing: Usually this is the longest stage before the vaccine is tried on humans and starts with detailed R&D. It includes preparing the roadmap, testing the vaccine on tissue culture etc. Finally the vaccine is tested on animals (mostly mice and monkeys) for examining its immune response.

This period has been much shortened in the case of coronavirus vaccines; yet, some preliminary studies about potential pros and cons, technological evaluation and then testing in animals cannot be avoided.

Phase I Safety Trials: Vaccine is given to a small number of people (usually below 100) to test safety and dosage while examining/ confirming that it stimulates the immune system.

Phase II Expanded Trials: Vaccine is given to a larger number of people (usually 100 - 300) in groups based on age etc. This phase further confirms the safety and immune response found in Phase I.

Phase III Efficacy Trials: Vaccine is given to a much higher number of people (in thousands) and  their results are compared with control population. Volunteers are needed for this stage as they have the risk to get infected if a proper immune response is not produced by their bodies. This stage is crucial and almost final, and determines the fate of the vaccine.

Combined Phases: So as to accelerate development of vaccines, testing in the next phase has been permitted for coronavirus vaccine while the previous phase is still on, under certain conditions.

At present, some vaccines in advance stages are under Phase I/II human trials and some in Phase II/ III trials.

Approval: The vaccine is submitted to the regulating authority of the country. Usually it takes many years, but coronavirus vaccines are likely to be approved within weeks. If the authority is satisfied with the trials conducted so far, it can approve emergency use even before final approval; this has actually started happening in the case of coronavirus.

Post Approval Phase: The testing continues even when the vaccine is being administered, so as to improve its efficacy and also to check whether its potency is going down with mutations in the virus and other factors. Besides the producer, the approving authority keeps doing concurrent tests of the vaccine.

 

As all labs and companies involved in coronavirus vaccine production seem to be rushing so as to remain competitive, a non-profit organization, Coalition for Epidemic Preparedness Innovations (CEPI), has come up to compare efficacy and other parameters of vaccines when they are mass-produced.

Will the COVID vaccine be effective for life?

Not likely.

 

The studies on the presence of antibodies in the blood of infected-and-recovered Covid patients have shown that their count diminishes fast over time. Some studies revealed that they become ineffective in around 3 months, but a study in August 2020 showed that they are sufficiently active till about 4 months. One can infer from these results that a vaccine will need to be re-administered in 3-4 months. However, much depends on the type of vaccine (e.g. protein-based/ based on attenuated virus/ non-Covid vaccine). It may also happen that vaccines produce a different reaction as compared to infection-induced immunity.

Most of the vaccines being developed will need a single-dose, but some will need 2/3 doses.Such vaccines will also behave differently from the single-dose vaccines.

All the vaccines under human trials are to be administered through injection. At least one vaccine is being tried for skin-level administration rather than deep injection.

How early can we expect vaccines against coronavirus?

The updated status of vaccines being developed worldwide as on 02 October, 2020 is as follows:

• Total number of vaccine candidates reported to WHO: 193
• Under pre-clinical trial stage: 151
• Under human trials: 43 [the following breakup will add up to more than 43 because of simultaneous trials] (data by NYTimes)
• Under human trial phase I: 28
• Under phase II: 14
• Under phase III: 11
• Approved for limited use: 5
  

The speed of development of vaccines depends on the type of vaccine and many external factors including success in different phases, availability of volunteers, efficiency in data processing and time management, and time taken in approval. 

It is expected that at least some of these candidates will succeed, and by the end of this year, one or two of them will start being sold at mass scale. The ones nearing the finishing line include those being developed by (i) AstraZeneca and Oxford University and (ii) Sinopharm. Many others are trying to catch up.

APPROVED FOR LIMITED USE, THOUGH IN TRIALS

A vaccine developed by CanSino Bio has been approved for use by the Chinese military though its advanced human trials are still being conducted. One by Sinovac (also a Chinese company) has also been approved for limited use. Its mass production has also been started, and it would be mass supplied to Indonesia immediately on final approval.

 

Another, developed by Gamaleya of Russia has been approved by the country's regulator without it going through Phase III trials. WHO, national governments and researchers are skeptical about the efficacy and safety of the vaccine, named Sputnik, as it has been tested in less than 200 individuals and has not met with the criteria universally agreed upon for clinical trials.

 

Two vaccines being produced by Chinese company Sinopharm and being developed by Wuhan Institute of Biological Products and Beijing Institute of Biological Products have been given permission for emergency use in the UAE. 

None of these 5 vaccines have passed Phase III trials yet.

PHASE III TRIALS

Now 11 vaccines are under Phase III trials. The notable ones (in which trials started early) are:

 

The vaccine being developed by AstraZeneca & Oxford University group seems to be ahead of others in the race. The Oxford University group's partner company, Serum Institute of India, is already producing he vaccine in millions of doses. You can expect emergency supply of this vaccine by October.

Chinese company Sinopharm has started Phase III trials on two vaccines. However, due to poor credibility of the Chinese system and also with the experience of their sub-standard supply of protective kits and face masks during early stages of COVID-19, their claim as well as benefit to the world community are being taken with a pinch of salt.

Murdoch Children's Research Institute in Australia is presently conducting Phase III trials on the existing BCG vaccine to check its efficacy for COVID.

The following companies have also started Phase III trials: Moderna, BioNTech.

OTHERS

Indian vaccine group of Bharat Biotech & ICMR has started Phase II trials and is fast-tracking all processes while meeting the global standards. They have been promised by the country's regulator that bureaucratic delays will not be allowed to come in the way in approvals.

We need to keep our fingers crossed till these vaccines actually come out of the labs, because even those in Phase III of human trials may fail or take a long time in approval if the results do not prove the required levels of safety and efficacy. Phase III trials of Moderna vaccine, one of the front-runners, had to be slightly delayed at the last stage. The Oxford University vaccine's Phase III trials had to be paused for some days as suspicious symptoms appeared in a volunteer. Inovio's vaccine trials were halted due to an issue with delivery mechanism.

VACCINE PRODUCTION

As said in the earlier section, a number of companies have already started production of vaccines in the hope that the ones being mass produced by them will eventually pass all stages of vaccine development. 

A number of rich nations are reported to be trying to book vaccines for their nationals, ignoring the needs of the poorer nations. US Operation Warp Speed programme is supporting seven vaccine candidates and is targeting to receive 300 million vaccine doses by January 2021. However, a group of experts are reported to have come to conclusion that availability of a vaccine to the masses is less likely before November 2021.

The COVID vaccine alliance (an initiative of WHO, GAVI and CEPI) proposes to deliver 2 billion vaccines to poor countries by end 2021.

Sources for updation: WHO, Nature, New York Times, GAVI, ICMR.