4.5 What progress has been made on a COVID-19 vaccine?
Dr Edward Parker
Vaccine Centre, LSHTM
A vaccine against SARS-CoV-2 (the virus responsible for COVID-19) has the potential to turn the tide of the devastating pandemic through which we are currently living
. Although the virus has already spread to every corner of the globe,
the vast majority of us are still susceptible: we lack the immunity
required to protect us from harm.
A safe and effective COVID-19 vaccine has the potential to change this, enabling us to resume our daily lives without the threat of illness. Scientists around the world are racing to develop such a vaccine. In this article, we will look at how far they have come.
How do you Develop a Vaccine?
What stages does a new vaccine have to pass through before we can use it?
First, there is the pre-clinical development phase. Here
, researchers determine exactly what the vaccine should consist of (its ‘formulation’) and then test the dose, safety, and effectiveness of this formulation in animals such as mice.
Next, the vaccine must go through clinical development. This involves testing it in
healthy volunteers to make sure it is
Clinical development is made up of
three phases of testing, as shown in the table below.
Crucially, phases II and III involve randomised, controlled trials
in which participants receive the test vaccine or a ‘control’ (either a placebo with no active ingredients, or a vaccine
for an unrelated
disease). By comparing infection rates in people who received the real vaccine versus the control, we can tell how well our new vaccine has worked.
Figure 1. A table showing the first three phases of clinical development.
Finally, once we know that a vaccine is safe and effective, it must be manufactured in large quantities. We also have to keep
monitoring safety and effectiveness when the vaccine starts being used in the real world (referred to as
Phase IV testing).
Developing a vaccine is a long, difficult, and expensive process. Research on a vaccine candidate may be halted if it fails to meet efficacy or safety requirements. A very small proportion of all vaccine candidates will progress all the way from pre-clinical testing to
When could we see a COVID-19 vaccine?
As of mid May 2020, there are at least 1
60 vaccine candidates in development for COVID-19
. This work is being carried out in over 25 countries
. The candidates include inactivated vaccines, live-attenuated vaccines,
and protein subunit vaccines (see
for more details about different vaccine types). Several novel vaccine types are also being tested, including DNA
] and RNA vaccines[
3]. These efforts were helped by the rapid sequencing of the SARS-CoV-2 genome, which was published by Chinese research groups on 10
Over 90% of the COVID-19 vaccine candidates are currently in the pre-clinical stage of development (i.e. not yet being tested in humans). However, 12 have progressed to clinical development and are being tested in healthy volunteers. To help people keep up with this ever-changing landscape, LSHTM’s Vaccine Centre have developed a COVID-19 vaccine tracker, which we currently update every
Figure 2. LSHTM’s COVID-19 vaccine tracker
Vaccine candidates currently being tested in large trials (>200 participants) are listed below. As you can see, groups around the world are trying out different types of vaccine. We
don't yet know which of these, if any, will provide protection against COVID-19.
Figure 3. The five largest COVID-19 vaccine clinical trials.
What happens next?
The development of a new vaccine usually takes around 10 years[1
]. For COVID-19, researchers across the globe are attempting to shorten this process, and remarkable progress has already been made. But there are many obstacles ahead and numerous candidates will drop out of the race at each phase of development.
We cannot predict when a COVID-19 vaccine will be ready with any certainty. Most experts hope that the process can be achieved in 12–18 months. If we are very fortunate, a vaccine might even be available sooner.
In the meantime, there are several key questions we need to answer about this novel virus:
Is it only antibodies that matter for protection or are other parts of the immune system also important?
Is there a certain amount of antibody that we need to protect us from illness?
If we can be re-infected, is the second illness just as severe as the first? Or do we also need to worry about antibodies potentially enhancing disease rather than preventing it? Antibody-mediated disease enhancement has been seen with vaccines against other viruses.
These factors will have an important influence on any future vaccine.
Antibody: Protein produced by our immune cells that bind
s to an antigen.
Clinical development: Development phase involving human volunteers.
accine: Consists of killed versions of the target pathogen. These versions are detected by our immune cells but cannot cause illness.
Non-replicating viral vector: A harmless virus that has been modified to display antigens from a different pathogen. For example, several vaccine candidates use adenoviruses (a type of common cold virus) as delivery systems to display SARS-CoV-2 proteins to our immune cells.
The vector viruses are able to
cells but cannot replicate or cause sustained infection.
Pre-clinical development: Development phase occurring in laboratories
before a vaccine is tested in humans, often
involving animal testing