How close are we to a vaccine for COVID-19?

A look at the different vaccines under development, and where they are in the pipeline

An effective vaccine against the coronavirus that causes COVID-19 is everyone's hope for a real return to normal life. More than 100 teams of scientists around the world are working to develop and test a vaccine against the virus SARS-CoV-2 as quickly as possible. They're employing a huge variety of strategies and technologies, including some that have never been used in an approved vaccine before.

"It's a very fascinating and kind of impressive effort," said Dr. Lynora Saxinger, an infectious disease specialist at the at the University of Alberta in Edmonton.

"It's absolutely crucial."

Even in countries that have had a devastating number of deaths from COVID-19, there is nowhere close to a level of "herd immunity" within the population preventing the disease from spreading exponentially if we go back to normal levels of social interaction, she said.

How far are we from the first SARS-CoV-2 vaccine?

Typically, it takes an average of more than 10 years for a vaccine to get from pre-clinical development (including animal testing) through three phases of clinical (human) trials to market registration.

The process has been fast-tracked for COVID-19. The first human vaccine trials began in March, just two months after the virus and disease were identified. And different phases of human trials are being run in an overlapping fashion instead of one at time — for example, Phase 2 might begin just a few weeks after the start of a six-month Phase 1 trial.

Still, officials, including the World Health Organization, have reassured the public that no steps will be skipped. That’s why Russia drew fierce criticism when it announced in mid-August that it was granting regulatory approval to a vaccine developed by Gamaleya Research Institute of Epidemiology after less than two months of human testing, with only two incomplete Phase 1 trials registered with the WHO.

Canada has a notably large number of vaccine candidates registered with the World Health Organization — at least eight.

Candidate vaccines in clinical trials

Note: Because of changes to the World Health Organization candidate vaccine document, we are no longer tracking phases that are completed and in progress. Instead we are marking each phase that the candidate has entered.
With data from the World Health Organisation

Multiple vaccines on the horizon?

Most vaccine candidates that make it to preclinical testing never make it to market (about 94 per cent fail, a 2013 study found). But in this case, with so many different vaccines under development, there may still end up being multiple vaccines for the coronavirus, possibly using different strategies, Saxinger predicts.

There are a number of potential advantages if that happens:

  • They'd be using different ingredients and manufacturing facilities and wouldn't be competing for resources — allowing for more vaccine production.
  • Different vaccines have different pros and cons. Some vaccines require more doses to be effective than others, while ease of manufacturing, testing and distribution varies.
  • Some vaccines may be more suitable for some populations than others, due to factors such as age or genetics.

Stephen Barr is associate professor of microbiology and immunology who is part of a COVID-19 vaccine development team at at Western University in London, Ont. He noted that the "best" vaccine in the end may not be best for everybody. "But the second one might be, for those that don't respond, right? So it's always good to have these backup vaccines as well or vaccines that can be used in parallel around the world."

Many teams are working on a COVID-19 vaccine using technologies that have been in development for decades, but have never yet been approved for wide-scale human use, such as DNA, RNA, and viral-vector vaccines. Many of those candidates are considered very promising, garnering huge amounts of funding and billions of preorders from some countries. In August, Canada announced deals to reserve millions of doses of RNA vaccines from Moderna and Pfizer, and also from Johnson & Johnson and Novavax.


Vaccine types:

Whole virus vaccines

These are the most traditional types of vaccine. They've been used for a long time, and most of us have had these kinds of vaccines.

Inactivated virus

In this case, the virus is grown in large quantities in cells, and then killed, often with a chemical, which is usually formaldehyde, but heat or radiation can also be used. Two kinds of flu vaccines are made this way, grown in either chicken eggs or mammalian cells.

Pros
  • Unlike live virus vaccines, it can even be given to people with weakened immune systems.
Cons
  • It doesn't lead to as strong an immune response as a live virus. Several doses, including boosters at regular intervals, are usually necessary.
  • It requires the virus to be grown in large quantities and that can take time and may not be as easy to scale up as other kinds of vaccines.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

Live, attenuated virus

In this case, viruses are also grown in cells, but instead of being killed they're genetically "weakened" so they can't infect cells and reproduce as effectively. Traditionally, this was done by getting the virus to grow in and adapt to an environment different than the one they normally infect. That's the approach used for vaccines such as varicella (chicken pox) or yellow fever. The SARS-CoV-2 vaccine candidates of this type use a high-tech genetic engineering approach called "codon deoptimization," where the virus is rebuilt from scratch, incorporating targeted mutations that weaken it. None of these vaccine prototypes for COVID-19 have made it to human trials.

Pros
  • Similar to real infection and usually provides long-lasting protection — sometimes lifelong — after one dose.
Cons
  • May not be suitable for people with weakened immune systems, long-term health problems, or people who've had organ transplants.
  • Live viruses need to be refrigerated, making them more difficult to transport and unusable in countries without access to refrigeration.
  • The virus must be grown in large quantities. That can take time and it may not be easy to scale up.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

Vaccines that target part of a virus

These types of vaccines don't contain entire viruses. They present parts of viruses, such as proteins or sugars, to your immune system to help it learn to recognize the virus and build an immune response.

In the case of SARS-CoV-2, the part of the virus that's typically targeted is the spike or "S" protein — the projections on its outer coat that make it look like a crown under a microscope ("corona" means "crown.") That's the protein the virus uses to bind to human cells, allowing it to enter.

What varies among different vaccine candidates is the way they make the spike protein and get it into the body — it may be injected directly, transported by a "carrier" virus that doesn't cause disease, or it may be manufactured by the human body itself using instructions encoded in DNA or RNA.

Virus-like particles

These are a special class of subunit vaccines, where the proteins are self-assembled into artificial particles that are intended to look like viruses to the human immune system. They bind to and enter cells like a virus, which is different from the way individual protein subunits do.

Some vaccines on the market that use VLPs include vaccines for HPV (human papilloma virus) and Hepatitis B.

Pros
  • Produce a stronger immune response than regular subunit vaccines.
  • Production is much faster than for traditional vaccines.
Cons
  • Ensuring stability and purification can add to production time.
  • Can be hard to produce in large quantities.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

Non-replicating viral vector

Viral vectors are "carrier" viruses that don't cause the disease you're vaccinating against, such as COVID-19, but can be engineered to carry a piece of viruses such as SARS-CoV-2. Non-replicating viral vectors are viruses that have been genetically engineered so they can't replicate and cause disease. Then they're further modified to produce the protein for the disease you want, such as the coronavirus spike protein, and injected into the body to provoke an immune response.

The viruses used by COVID-19 vaccine candidates include adenoviruses, MVA (modified vaccinia ankara, a weakened pox virus), parainfluenza and rabies.

Pros
  • Generates more powerful immune response than subunit proteins.
  • Some don't have to be stored at very low temperatures (according to China-based company CanSino), so they're viable for use in resource-limited tropical areas.
Cons
  • People who have already been exposed to the viral vector, such as adenovirus, may be resistant.
  • Harder to scale up than protein or DNA because a virus still needs to be grown.
  • Because each virus can only infect one cell, large quantities of the virus need to be grown and injected, adding to production time.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

Replicating viral vector

These are "carrier" viruses that can replicate in the body, but are either weakened or don't cause any symptoms in humans. Like non-replicating viral vectors, they're modified to produce a protein from the virus you want to protect against, such as the spike protein from SARS-CoV-2.

The replicating viral vectors used in COVID-19 vaccine candidates include weakened versions of influenza and measles, as well viruses that cause animal diseases such as horsepox and VSV (Vesicular stomatitis virus).

Pros
  • Closely mimics a real infection and induces a stronger, more widespread immune response.
  • Because it can replicate, much less virus needs to be injected as a vaccine to induce a good response.
  • That also means less needs to be grown to produce the vaccine, cutting the cost, time and labour needed compared to whole virus and non-replicating viral vector vaccines.
Cons
  • Requires more testing before approval than protein or nucleic acid-based vaccines, adding to development time.
  • Needs to be stored and transported at cool temperatures to keep the virus alive, which may make it harder to distribute in warmer parts of the developing world.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

RNA

With RNA vaccines, what's injected into the body is simply the genetic instructions to make a viral protein such as the spike protein. Cells in your body then use the instructions to make the protein inside the body for your immune cells to see and respond to.

Pros
  • No virus is needed to make the vaccine, cutting production time compared to conventional vaccines.
Cons
  • Don't always produce a strong immune response compared to whole viruses, and may require adjuvants.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

DNA

This is very similar to the RNA vaccines, except that DNA is used instead of RNA. It's often delivered as a ring of DNA called a plasmid.

That enters the cell, and the cell produces the virus protein.

Pros
  • Quick and relatively inexpensive to manufacture in large quantities.
  • Shelf stable and doesn't require freezing in storage and transport.
  • Easy to switch to different gene/virus, and you can combine multiple in single vial.
Cons
  • Requires adjuvants for a good response.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

Protein subunit

With this type of vaccine, the protein is made outside the body. Traditionally, this was done by breaking whole viruses into pieces using detergent or a solvent such as ether.

However, this can now be done with "recombinant" genetic technology, where the gene for a protein is inserted into another organism to grow the protein in large quantities.

Pros
  • Can be produced more quickly than live vaccines.
Cons
  • Doesn't generate as strong an immune response as whole virus vaccines.
    A compound called an adjuvant needs to be included to boost a patient's immune response.
  • Can't be scaled up as quickly as production of RNA or DNA vaccines.
Clinical trials and Canadian candidates
All candidate vaccines in clinical trials

Lots of Canadian candidates

As mentioned earlier, Canada currently has at least seven vaccine candidates under development, with Canadian involvement in the development of some others. Saxinger said that maximizes the impact of the expertise we have, from work on diseases such as Ebola, SARS and MERS.

Developing and producing vaccines here at home could also give Canada more control over when Canadians can get the vaccine, and who can be prioritized, given that there will likely be huge demand for the vaccine from countries around the world.

"I don't think we want to rely on others, hoping they will remember us," said Volker Gerdts, director and CEO of VIDO-Intervac at the University of Saskatchewan in Saskatoon, one of the Canadian teams developing a SARS-CoV-2 vaccine. The current race for a vaccine underscores why it's important for countries like Canada to be self-sufficient, he added.

Canadian vaccine candidates

Correction: A previous version of this story said RNA vaccines require adjuvants. In fact, this is not always the case, as RNA itself can act as an adjuvant.

Note: Because of changes to the World Health Organization candidate vaccine document, we will no longer split Phase 2 and Phase 3 into two stages.