The world is eagerly awaiting one or more vaccines to protect us against the SARS-CoV-2 virus. We will only be able to fully resume our lives when we are immune to the infection. According to the World Health Organisation, around 150 vaccines are currently in development. Vaccinologist Corinne Vandermeulen of the Leuven University Vaccinology Centre (LUVAC) at KU Leuven lists the different types.
The goal of a vaccine is always the same: activating the immune system so that it builds up sufficient protection and can react effectively if the virus enters the body. "A vaccine uses natural processes that are already present in the body," says Professor Vandermeulen. "In fact, it acts as a driving force to initiate these processes in a controlled way."
Vaccines don’t just protect the person who receives them. "By offering vaccines to everybody, we create herd immunity. This allows us to protect those people who are vulnerable and cannot be vaccinated or people who do not respond to a vaccine. It’s a nice principle of solidarity that can only be achieved through vaccination," says Professor Vandermeulen.
Developing a vaccine is precision work: each vaccine needs to be specifically developed for the microbe - in this case a virus - against which we want to build up protection. That’s why virologists had to wait for samples or the genetic code of the coronavirus before they could start working on a vaccine.
Every vaccine contains at least one antigen: a molecule that can trigger an immune reaction. This may consist of complete (inactive) virus particles or pieces of them. Some vaccines that are currently in development, for instance, only use the club-shaped spikes or crowns to which the coronavirus owes its name. To understand the choice for these protrusions, it’s important to know that viruses (only) consist of genetic material in a protein casing: they need living cells to be able to multiply. The protrusions of coronaviruses attach themselves to the wall of healthy cells. This allows the genetic material of the virus to enter the cell. The cell deciphers the code, which contains the instruction to multiply the virus. If antibodies organise themselves around these protrusions, the virus can’t attach itself to cells and, therefore, can’t multiply. The T-cells, the ’army’ of our immune system, can then get rid of the virus.
There are many elements to take into account when choosing a particular type of vaccine. The number of doses, for example, is crucial: ideally, the vaccine only needs to be administered once. The content of the vaccine also needs carefully fine-tuning: the immune system must be able to mobilise enough antibodies in our mucous membranes. This way, the antibodies can block the virus immediately, preventing us from becoming infected. This is called sterile immunity, and it’s the gold standard for all vaccines.
In total, there are around nine different types of vaccines. Below, we discuss the types that are used to prevent infections with viruses. If you want to know more about the vaccines being developed against COVID-19 by different laboratories: the WHO overview shows which lab is working on which type of vaccine.
Professor Vandermeulen: "The virus is exposed to varying temperatures in cell cultures, which weakens it and prevents it from making people ill. However, the virus can still multiply in the body and, thus, spread a larger dose of antigens. Examples of live-attenuated vaccines include those against yellow fever, rubella or measles."
Advantage : more antigens ensure a stronger immune system response than you would get using a dead virus.
Disadvantage : these vaccines can’t be used in people with a suppressed immune system. These people can be protected by herd immunity: if 90 to 95 per cent of people are vaccinated, the spread of the virus will be very limited.
Professor Vandermeulen: "The basis of these vaccines is a known virus that doesn’t cause diseases in humans. This can be an innocent virus or a live-attenuated vaccine virus (the virus used in another vaccine). An antigen or the genetic code of an antigen is introduced into the virus. At KU Leuven, a team led by Professor Johan Neyts is developing a vector vaccine against SARS-CoV-2 on the basis of the virus contained in the yellow fever vaccine."
Advantage : you can use known vaccines that have already proven their efficacy. The research phase can also be carried out faster because you’re dealing with known technologies.
Disadvantage : as it concerns a genetically modified vaccine, more tests are needed before a clinical study can be initiated. Moreover, similarly to other attenuated vaccines, these vaccines can’t be used in people with a suppressed immune system.
Fully inactivated vaccine
Professor Vandermeulen: "This vaccine is made with a dead version of the virus that is being fought. The virus is killed by heating it or by bringing it into contact with a substance that is harmful to the virus, for example formaldehyde. This technique was frequently used to make vaccines in the past, such as the vaccine against polio."
Advantage : the virus is dead and can no longer cause disease, but at the same time all the antigens are present. As such, it offers a broad protection against the virus.
Disadvantage : as the virus has been made inactive and is unable to multiply in the body, multiple doses of the vaccine are usually needed.
Professor Vandermeulen: "For this vaccine, the virus is cut into pieces. All pieces of the virus are present, but they can’t cause disease. The only example of this kind of vaccine is the flu vaccine."
Advantage : the virus is inactive, while all elements remain present.
Disadvantage : it’s difficult to determine the right dose. Moreover, this type of vaccine is not easy to produce.
Professor Vandermeulen: "Instead of using a complete virus, you can also use a piece of the virus as an antigen. For this process, a protein from the capsule of the virus is often used: in coronaviruses, this is the protein from the protrusions on the virus (the so-called spike protein). The hepatitis B vaccine is the first vaccine that was developed this way. It wasn’t until this century that we found the right techniques to specifically detect the suitable antigens of a virus (or bacterium)."
Advantage : it’s easier and, therefore, faster to produce a single protein than to grow a complete virus.
Disadvantage : as only one antigen is used, you either need multiple doses or an adjuvant to induce a good immune response.
Viral-like particle vaccine
Professor Vandermeulen: "This is a variant of the protein vaccine. The antigens are proteins that are composed in such a way that they form an empty shell. This means they resemble the virus, but don’t contain its genetic material. One vaccine against this type is currently on the market: the vaccine against the human papilloma virus."
Advantage : these vaccines give a stronger signal to the immune system than when the antigens are in a solution.
Disadvantage : they’re not easy to produce: the proteins need to be carefully composed to induce a good immune response. As only one or a few antigens are used, you need either multiple doses or an adjuvant to induce a good immune response.
Vaccines on the basis of DNA or RNA
Professor Vandermeulen: "DNA and RNA vaccines don’t contain the antigen itself, but rather its genetic code. This code needs to be able to get into a cell or cell nucleus, because the cell has to decipher the genetic code in order to make antigens."
Professor Vandermeulen: "DNA vaccines need to get into the nucleus. This can be done by administering a small electric shock when the vaccine is administered. But that means that you need extra material, something developing countries cannot afford. This type of vaccine could not only be used preventively, but also as a therapeutic vaccine to treat ill patients. However, there are currently no DNA vaccines for humans on the market."
Advantage : as they use natural cell processes, they’re easy to produce.
Disadvantage : it’s impossible to provide DNA vaccines worldwide: the device needed to administer the electric pulses is too expensive.
"In RNA vaccines, the genetic code is contained in a fat or lipid solution. The lipids fuse with the cell surface, allowing the RNA code to get into the cell. Determining the correct lipid composition requires precision work. It’s a completely new technique that has only been around for a few years. Therefore, there are no RNA vaccines on the market yet."
Advantage : just like DNA vaccines, RNA vaccines are easy to produce.
Disadvantage : as they’re new, it is still unclear whether these vaccines actually work well.
As we get older, our immune system becomes less effective. When that’s the case, an inactivated or protein vaccine only has a chance of succeeding when it’s administered in a very high dose. However, the available amount of antigens is limited. That’s why excipients or adjuvants are used: they enhance the effect of the vaccine without having to increase the dose of the antigen. The most commonly used adjuvant is aluminium hydroxide, which is very safe and has been used for over 50 years. In the meantime, new adjuvants have come onto the market that can boost parts of the immune system.