The Battle in our Bodies: Coronavirus, Immunity and the Role of Vaccines.

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 allow 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 (such as macrophages) 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. Data so far shows infection may only provide protective immunity for 6-12 months, but this varies from person to person depending on the type of infection they had.

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. Some of the newer vaccines technologies work differently in the way that they present the target ‘antigen’ to the host’s immune system compared to more traditional approaches.

Traditional vaccines present antigens directly to the immune system. These antigens might be in the form of manufactured proteins (recombinant protein vaccines) or weakened versions of viruses or bacteria (known as live attenuated vaccines). These approaches often produce a strong immune response but can be slow to develop and may be unsuitable for certain people.

Newer technologies use part of the viruses' genetic code that produces the spike protein rather than the antigen directly. Scientists use this code to construct vaccines, which instruct cells of the human body to produce the spike protein. These types of vaccines are quicker to develop but are 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 and AstraZeneca uses one of these newer technologies. 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. This means they can be safely used in many individuals who cannot have certain other types of vaccines. It is very easy to adapt these viral vectors to make new vaccines. Before SARS-CoV-2 we used the same technology for vaccines for other diseases including HIV, Malaria, and Ebola.

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 the Oxford-AstraZeneca vaccine a 12 week interval appears to achieve this balance 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.

Data so far suggests that the Oxford-AstraZeneca vaccine is highly effective at preventing hospitalisation, effective at preventing mild to moderate disease in most individuals and reduces transmission of the virus.

Our work isn’t yet finished. We need to make enough vaccine for everyone who needs it and make sure it gets to them. The Oxford-AstraZeneca vaccine is a vaccine for the world. It is being manufactured around the world and will be always be provided on a non-for profit basis to the world’s poorest countries. Vaccines save lives, but only if people get them.

The Battle in our Bodies: Coronavirus, Immunity and the Role of Vaccines.

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