Even in the experiments of Edward Jenner more than two centuries ago and Louis Pasteur after him, it was apparent that immunisation could protect people against the ravages of disease. Jenner found that inoculating people with a small dose of cowpox meant they were less susceptible to the related, far more serious disease of smallpox. Around 100 years later, Pasteur used doses of attenuated – or weakened – rabies virus to protect people who had been bitten by rabid animals.
Neither had much understanding of why the vaccines they had pioneered were working though. As we have learned more about pathogens and how our immune systems protect us against them, it has become clear that vaccines are among the most powerful tools we have against viruses.
It is why health authorities all over the world are now embarking on what are likely to be the largest vaccination programmes in the history of many countries. Vaccines are perhaps our best hope of controlling the Covid-19 pandemic (PDF), but it is perhaps worth looking at why that is.
Harnessing the immune response
The principle underlying all vaccines is that they prime our immune systems to recognise and attack invading disease-causing organisms. Our bodies naturally respond to bacteria, parasites, fungi and viruses that might do us harm with a cascade of defences. In the case of viruses, these are usually triggered within a few hours of infection by chemical signals released from our cells as they come under attack. This activates what is known as the innate immune response, which tries to directly inhibit the growth and spread of the virus within cells.
At the same time our “acquired immune response” is also mobilised. This produces the long term memory of our immune systems, through white blood cells known as B lymphocytes and T lymphocytes. The B lymphocytes recognise distinctive parts of a virus and start producing antibodies against it, and cells that have become infected with the virus can be destroyed by a type of T lymphocytes known as cytotoxic T cells, helping to eliminate the virus. Another type of T lymphocyte called Helper T cells increase the activity and effectiveness of both B lymphocytes and cytotoxic T cells.
But when the immune system first meets a virus it hasn’t seen before, the amount of antibody and the number of T-cells that recognise it are very low. It usually takes around a week for enough to be produced to mount an effective immune response. In a normal infection, this lag can be crucial as it gives the virus time to replicate and spread to other people. But any re-exposure to the same virus triggers a ‘secondary’ immune response, which is quicker and higher than the first response.
Vaccines allow us to trigger this secondary acquired immune response by using viruses or bacteria, or parts of them, that have been modified or inactivated in some way so they can no longer cause disease. A new class of vaccine being deployed against Covid-19 uses mRNA – a small piece of genetic instructions that teach our cells to produce a tiny but important part of the virus themselves. In both cases, this then helps train the immune system to recognise and memorise the virus so that when it encounters it for real, its immune response will be fast and decisive.
How we know they work
Even with this understanding of the immune system, there are still really only two meaningful measures of the efficacy of a vaccine. The first is its ability to prevent and minimise the symptoms of disease, while the second is if it can reduce transmission or spread. In most cases that can be done through observation of people who receive the vaccine during clinical trials.
It is also possible to measure the amount of antibodies or T-cells in a person’s blood serum, but the levels of these do not always correlate with protection against a disease. Part of the reason for this is that testing antibodies against a virus in the laboratory does not replicate all of the mechanisms by which it may kill a virus in the body. Other parts of the immune system such as the T cells contribute to protection, and so a person can be protected against the disease even if tests for antibodies in the laboratory appear not to produce much of a result.
With Covid-19 we have seen encouraging antibody and T cell responses in the laboratory from samples taken from people who have received vaccines against the virus. But we should not be too alarmed by studies that suggest new variants of the virus that causes Covid-19 are showing signs of being able to evade neutralising antibodies – those antibodies that bind to the virus to prevent it infecting cells. As yet we don’t have any tests to show how these new variants cope with the other components of the immune response that can be primed by vaccines.
Why we need boosters
Even if a vaccine is effective at preventing disease and reducing transmission, it is rare it will completely prevent people from being reinfected. It is perhaps a common misconception that once someone has received a vaccine they then cannot catch that disease. It can take a week or two for adequate immunity to develop after the first dose of a vaccine. Often a second dose – or booster – is needed to get a stronger immune response and one that lasts longer (PDF).
But even when someone has been fully vaccinated, viruses can still get into their body and begin infecting cells. An effective vaccine will help the immune system to fight back against the virus before it has a chance to replicate itself in earnest. By reducing the replication of the virus within the body, it also reduces both the appearance of the disease and hampers the virus's ability to spread to other people.
How long does immunity last?
Unfortunately, immunity can wane with time. Some vaccines provide long lasting immunity that can persist for decades or even whole lifetimes. But with some diseases it can fade more quickly and this seems to be particularly pronounced with some respiratory viruses, including the coronaviruses (PDF). The reasons why immunity fades faster for some viruses than others is still not well understood and it is also still too early to tell how long immunity will last in those who receive the Covid-19 vaccines.
Of course, the Covid-19 virus could mutate to the point where it can escape immunity induced by vaccines or previous infections. This happens with influenza, which is why we regularly see waves of epidemics despite annual vaccination programmes. But we could also protect ourselves against this by producing vaccines that target more than one part of the virus. The chance of the virus then picking up enough mutations simultaneously to escape this approach is far lower. But the development of such vaccines will require more investment, time and testing.
Getting to herd immunity
To really control a virus like Covid-19, we will need a degree of herd immunity (PDF). This is the point where enough people have immunity against the virus that it becomes unable to sustain enough infections to cause an epidemic. You might still get isolated outbreaks, but it then can’t spread further in the population. To achieve this largely depends on how infectious the virus is – something we measure with the R0. For a disease like measles, which is normally regarded as having an R0 of more than 10, we need 90% of the population to be immune. Covid-19 has an R0 of somewhere between 2-4 (PDF), which means we would need 60-70% of the population to be immune, although estimates vary depending on the country and public health measures in place (PDF).
It is well accepted that to reach this level through natural infection with Covid-19 would entail an unacceptable degree of illness and death. Vaccination offers us a way of doing it without that.
To date, vaccines have enabled humanity to eradicate three particularly nasty viruses that affect humans – one responsible for smallpox and two types of polio virus. A third type of polio virus is on the brink of being stamped out too.
In the face of the 200 plus viruses that cause disease in humans, eradicating just three seems like a small victory. But vaccines also bring a better quality of life to millions of people by protecting them from many of those viral diseases that still persist, such as yellow fever, hepatitis B, human papilloma virus, measles, mumps, etc. Vaccines have also brought bacterial illnesses once rampant within populations – such as tetanus, diphtheria, whooping cough and meningococcal disease – under control in many countries.
As vaccine technology and our knowledge of the immune response continues to improve, that protection should continue to grow too.
Find out more
Join Professor Brian Cox and a panel of expert speakers, including Professor Charles Bangham, to explore whether vaccines will provide the solution to the coronavirus pandemic.