The virus that causes Covid-19 disease (SARS-CoV-2 to give it its full name) is a member the Coronavirus family and is responsible for the current ongoing ‘pandemic’ (a global disease outbreak).
Coronavirus like most viruses is very simple. It has an outer shell (envelope) which protects its genetic material inside (Ribonucleic Acid, RNA) and is covered in spike proteins which allow the virus to infect cells of the human body.
Like all viruses, coronavirus cannot replicate without a host cell. SARS-CoV-2 uses its spike protein, like a key, to gain entry to cells using a specific receptor (called ACE2 in this case), which acts like the lock to the door of the cell.
Once inside, the virus hijacks host cell machinery to copy its genetic material and manufacture its shell and spikes, which in combination form new viruses. These eventually rupture the host cell and go on to infect more cells progressing the infection.
The infection usually starts in the upper respiratory tract (nose and throat) and gradually moves down to the lower respiratory tract (lungs). However, ACE2 is found on many different cells of the body, so the virus has the potential to cause a systemic infection (throughout the body) and more serious disease. In fact, the amount of ACE2 expression has been linked to a variety of risk factors such as age (children have less ACE2, adults more) and sex (men have more ACE2 than women).
Luckily, we have an immune system and for most of us this can slow and stop the infection before it gets too serious.
T cells and antibodies are important active components of the immune system that can recognise and destroy viruses. Both T cells and antibodies can recognise markers or ‘antigens’ that are specific to individual pathogens (disease causing agents), such as the coronavirus spike protein.
Some T cells (Killer T cells) recognise cells infected with a virus and destroy them, whilst other T cells (Helper T cells) help direct the other immune cells of the body to fight the virus. The receptors on the surface of T cells help them with these roles by allowing them to recognise antigens presented to them by other cells.
Antibodies are Y shaped proteins that are produced by immune cells called B cells.
Antibodies can stick to the spike protein on the virus, which can stop the virus entering cells and replicating within. They stick to the key so it cannot fit the lock. Such antibodies are known as neutralising antibodies. Antibodies can also make it easier for other cells of the immune system to bind to, swallow and destroy the virus (a process called phagocytosis).
After an infection is cleared, the body retains an immune memory of the Coronavirus spike protein in the form of specialised populations of B cells and T cells. In theory, if the body encounters the virus again it can respond quickly and in the best-case scenario can prevent infection completely.
However, if the immune response is not very strong, it may only reduce the impact of the infection or even do nothing at all. It may be that to achieve protection through natural exposure, you need more than one exposure to the virus, but, at this time, we really don’t know.
Vaccines are arguably one of the most effective health interventions available for controlling any particular disease. They stimulate our immune systems to provide protection without the need for natural infection. Scientists around the world are working to develop and test new vaccines for Covid-19.
There are a number of different approaches to developing vaccines against Covid-19, but we can group them into 2 broad categories based around the different ways that they present the target ‘antigen’ to the host’s immune system.
The first type of approach uses the COVID-19 spike protein directly to educate the immune system. The protein or antigen can be produced in the laboratory (known as a recombinant protein vaccine). Alternatively, scientists can use a weakened version of the virus (known as a live attenuated vaccine). These approaches often produce a strong immune response but can sometimes be more reactogenic (has more side effects).
The second approach uses the part of the viruses' genetic code that produces the spike protein. Scientists use this code to construct vaccines, which instruct cells of the human body to produce the spike protein. This approach is generally considered to produce less side effects but is a lot newer, so it is not always known how strong the immune response will be to the vaccine.
The vaccine being developed by the University of Oxford falls into the second group. Scientists have taken the genetic sequence of the SARS-CoV-2 spike protein and inserted it into a common cold virus that infects chimpanzees, an Adenenovirus called ChAdOx1.
When this virus infects human cells, it encourages them to make the SARS-Cov-2 spike protein. This helps the body produce an immune response which can respond if it encounters the actual SARS-CoV-2 virus.
The cold virus itself has been modified so that it cannot naturally replicate in human cells and cause disease. Adenovirus vaccines are currently also in development for other diseases like HIV, Malaria, and Ebola and have been tested on tens of thousands of people. They are considered a universally safe approach for vaccination. The Oxford COVID-19 vaccine is nonetheless undergoing extensive clinical trials to test how safe and effective it is.
Like an infection, a vaccine encourages the body to produce both antibody-producing B cells and T cells. Some vaccines may be more effective at producing one type of cell than the other. We hope that with the right vaccine, we can reach a protective level of antibodies or T cells (or a combination of both) more quickly and safely than through natural infection alone. Vaccines are usually designed so that they also produce a more robust immune memory than a natural infection does.
Sometimes giving just one vaccine is not enough to achieve protection. In such cases, an additional 'booster' vaccine is used. Using clinical trials, researchers can test the optimal timing between the first and second vaccination to achieve a level of protection as quickly as possible, whilst maintaining the long-lasting memory as well.
For some vaccines, further boosts (additional vaccinations) might be needed in subsequent years to keep the immune response high enough to maintain protection. Boosts may be particularly important in older individuals (or those with a weaker immune responses), as their immune memory tends to decline faster than younger, healthier individuals.
So far, we have shown that the Oxford vaccine is safe for our volunteers and that it produces an immune response. The initial vaccination has produced good numbers of T cells and neutralising antibodies.
After a second vaccination we don’t see many more T cells, but we see neutralising antibodies in pretty much all our volunteers. We are now conducting clinical trials in tens of thousands of volunteers all around the world to assess whether these immune responses can protect people against infection.