May 21, 2020 | News | Living with MS

Vaccines use different approaches to target COVID-19

Over 100 vaccines are now in various stages of development to prevent COVID-19 infection and a few vaccine candidates have reported some promising preliminary results. A wide range of candidates is needed because there is an urgent need to find an effective vaccine, little is known about the virus and it isn’t clear what the best approach will be.

The idea behind a vaccine is to educate a person’s immune system so it recognizes and more efficiently deals with an infection. An infection triggers a response from the innate immune system, in which immune cells (such as macrophages and dendritic cells) detect a foreign intruder and attack it. This early line of defence is crude and not very targeted. The problem is that this early immune reaction involves a variety of non-specific responses – such as fever and inflammation – that can cause collateral damage. In the case of COVID-19, these responses can end up being more harmful than the infection itself and are often the underlying cause of death due to secondary complications.

In humans, the initial immune reaction will activate a more targeted response that is specific to the pathogen. This involves T cells, which coordinate the attack, and B cells, which produce antibodies specific to the infection. The presence of antibodies in the bloodstream generally indicate that the person had the infection and is now “immune”.

The two key challenges to developing a vaccine are to identify the right antigen(s) that will stimulate an immune response; and to efficiently deliver that antigen to the right place. An antigen is typically a protein fragment that is specific to the virus. This enables the immune system to identify what is a virus component in the confusion of other protein fragments in the body. Fortunately, a great deal has been learned about the virus that causes COVID-19 (called SARS-COV-2). A key feature of the virus is that its surface is covered in spikes, which allow the virus to attach to cells in the body. Human cells don’t have these spikes. If the immune system can learn to recognize those spikes, it’s certain that the thing attached to that spike is the virus.

The two vaccine candidates that have been in the news recently – one produced by a company called Moderna, the other by researchers at Oxford University – use spike protein as the antigen. Human trials for these vaccines have already begun. A China-Canada collaboration is also working on this type of vaccine. However, it isn’t known if an immune response to spike protein will be sufficient to prevent COVID-19 infection. So some companies, such as BioNTech in collaboration with Pfizer, are using an assortment of viral proteins in the hope that this will stimulate a better immune response. The first people received a test dose of this vaccine in April.

The second challenge is delivering the antigen to the right place. One approach is to use a different virus (one that doesn’t cause illness) as the delivery vehicle (called a vector). A virus is essentially an outer coating that protects the virus’ own genetic material. But there’s some room to spare, so the viral vector can be packed with additional genetic material, such as genes that produce CoV-2 spike protein. As the benign virus reproduces, it also produces CoV-2 proteins that teach the immune response to recognize CoV-2. This will make the body’s response to an actual CoV-2 infection much faster and more efficient. The Oxford group had already developed this technology for other vaccines, so when the pandemic hit, the delivery method was already in place. They just had to wait until more was known about the CoV-2’s genome so they could pack their vector with the right antigen.

A slightly different strategy is to have the viral vector infect specific immune cells, which will then signal to T cells and antibodies to attack the CoV-2 proteins. Two vaccines in development in China are using this approach.

The optimal antigen to stimulate an immune response isn’t known, so some vaccine candidates are harkening back to an older approach – using an inactivated version of the pathogen. This uses the whole virus, not just bits of protein, but the virus has been weakened so it can no longer cause disease. This is how vaccines for polio and influenza were developed. A company in China is currently working on an inactivated CoV-2 vaccine.

The first step in vaccine development is to ensure that the treatment is safe – it doesn’t cause the illness and it doesn’t induce an allergic reaction. Two vaccines may have already reached this milestone although further safety testing will be needed. The second step is to see if the vaccine stimulates the body to produce a sufficient number of antibodies. The third step is to do a challenge study – expose vaccinated people to CoV-2 to see if they develop COVID-19 (or at least a milder form of the disease). The likelihood of failure at any point is high. That is why so many approaches are needed, and why vaccine development is such a time-consuming process. But with over 100 vaccines being tested, the hope is that an effective vaccine will become available within a year.

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