Making a COVID-19 vaccine
Updated: May 7
What are the top candidates for a COVID-19 vaccine and what kind of timelines are we looking at for approval?
There has been a huge effort to develop a COVID-19 vaccine in record-breaking time. The Coalition for Epidemic Preparedness Innovations (CEPI) is investing in several biotech companies in order to reach their goal of having 1 million doses of vaccine available in the next 12-18 months. Having a vaccine out in 18 months is extremely ambitious. The fastest vaccine ever to be made was for ebola and it took 5 years. Usually, vaccines take between 10-15 years to make due to the long process they have to go through: from several years of research and development, to developing a prototype, to extensive clinical trials to test safety and efficacy and lastly to mass production and distribution.
Traditional vaccines work by mimicking a virus sufficiently to trick the body into thinking it’s been infected, causing the body to make antibodies against that virus. This makes you immune to a real infection. Vaccines can mimic the real virus in different ways: 1) live-attenuated vaccines are viruses that are modified so they don’t cause a disease, 2) inactivated viruses which don’t replicate, and 3) subunit vaccines; these take advantage of the piece of the virus that causes the immune response.
The current WHO landscape of candidate COVID-19 vaccines highlights how all of these different approaches are being explored by different biotech companies. For example, EpiVax has sped up the process to make a subunit vaccine through computational models that can go from the genetic sequence of the virus to predicting which bit would make a good vaccine in a matter of hours. They are currently making the subunit and plan to use it in first clinical trials in 3 months. Janssen (owned by Johnson & Johnson) hopes to have their vaccine candidate in clinical trials in September. Their approach, which was used to make a successful Ebola vaccine, uses a harmless version of another virus called an adenovirus. The adenovirus is engineered to carry genetic information coding for the SARS-CoV-2 subunit which triggers an immune response. When a patient is dosed with the modified adenovirus, their cells will generate SARS-CoV-2 subunits, which will then trigger an immune response and immunity.
Getting cells to read genetic ‘instructions’ to make their own vaccines is an approach that is being widely explored in response to COVID-19, mainly because making genetic material is much faster than making the protein of the vaccine. As an example, Inovio claimed to have designed their DNA-based vaccine within 3 hours of receiving the viral sequence, and plan to go into human trials this month. Delivering the genetic material into the body poses a challenge - our bloodstream is full of enzymes that quickly cut up DNA or RNA. Different companies employ different approaches from applying small electrical currents to packaging the genetic material to protect it.
The furthest the COVID-19 vaccines have progressed so far are from preclinical to Phase I trials. These include Moderna with their RNA-based vaccine which they are testing the safety of their drug in various locations in the US with initial results expected to come out in June. Another company is CanSino Biological testing their adenovirus-based vaccine in Wuhan with first results to come out at the end of the year. The number of candidates moving into these initial clinical trials is rapidly increasing. Although this step is exciting, it is only the beginning of the vaccine’s journey of proving itself to be a worthy investment. Some groups are exploring if we can repurpose existing vaccines used for other diseases such as tuberculosis to see if they can also protect against COVID-19, a method that if successful would avoid these initial Phase I safety tests. Ultimately all of these candidates will have to prove their efficacy at protecting us from COVID-19 as well as their safety, and these tests may be harder to overcome.
To date, there are over 40 candidate COVID-19 vaccines in development. At this stage it is impossible to tell which ones will be successful. This is because of the number of different obstacles that stand between concept and use, and the challenges that will arise from each stage are largely unforeseeable and depend on the exact nature of each of the candidate vaccines. For example, the RNA-based vaccines have been highly successful so far in going from development to clinical trials, but, as there are no existing RNA-based vaccines, it is very hard to predict any challenges that may arise as the candidate vaccine progresses through the various stages of development.
The scalability of the production of the vaccines will also be an important factor to be able to make enough to run large clinical trials and to reach all the people that will need the vaccine after it is approved. How the vaccines are manufactured varies widely and depends on the technology the company is using, for example Janssen have set up a large bioreactor system in order to quickly grow adenoviruses. As a small change in the manufacturing process can affect the final vaccine product, this process needs to be optimised before clinical trials (i.e if you change how you manufacture the vaccine, you’ll have to re-do the clinical trials).
As the race continues and more data is collected on how successful these candidates prove to be when actually used in humans the ‘winners’ might become clearer.
NB: Going from concept to drug is a long and convoluted journey, shaped not only by science but also economics and politics. Check out this post for an overview of the drug development process and this post (coming soon) about potential pitfalls new COVID-19 vaccines need to avoid in order to be successful. The response to COVID-19 includes not only the race for a vaccine, but also the development of medicines to treat people who are infected and help them recover - post coming soon.
This field is rapidly evolving and the information shown here is correct at the date of publishing. More recently Nature has made some amazing graphics that illustrate the different types of vaccines undergoing development - check it out here