How vaccines work: training the immune system without the disease

When a germ enters the body, the immune system's first line of defence responds in minutes to hours, but in a general way. The second line, called adaptive immunity, takes days to build a response aimed at the particular invader: B cells make antibodies that bind to it, and T cells kill infected cells or coordinate the response. In the first encounter this is slow, and the germ may do damage before the body has caught up.

The important part is what happens afterwards. Some of these cells survive as memory cells, which can stay for years or a lifetime and respond within hours when the same germ appears again. A vaccine produces that memory without the dangers of the disease.

Vaccines use several different approaches to show the immune system the antigen.

• Live attenuated vaccines use a weakened form of the germ, as in the measles, mumps and rubella vaccine, the BCG vaccine against tuberculosis, and the oral polio vaccine.
• Inactivated vaccines use a killed germ, as in the injected polio vaccine and some hepatitis A vaccines.
• Subunit and conjugate vaccines use a part of the germ, such as a protein or a sugar coat, as in hepatitis B and several vaccines against bacterial infections.
• Toxoid vaccines use a harmless form of a toxin made by the germ, as in tetanus and diphtheria vaccines.
• mRNA and viral vector vaccines give the body's cells instructions to make a single protein of the germ, so that the immune system can learn to recognise it. Several COVID-19 vaccines used these methods.

Some vaccines contain an adjuvant, a substance such as an aluminium salt that strengthens the immune response. Many need more than one dose, or later boosters, because the protection fades over time. Some germs also change, which is why influenza vaccines are updated each year to match the strains that are circulating.

A germ spreads when each infected person passes it on to at least one other. If enough people in a community are immune, most of those chains break, and the germ finds it difficult to spread at all. The share that is needed depends on how contagious the germ is. For measles, one of the most contagious diseases known, about 95 per cent immunity is usually needed. This indirect protection matters most for babies who are too young to be vaccinated and for people whose immune systems are weak.

Before a vaccine is approved, it goes through laboratory studies and then three phases of trials in people, beginning with small groups and ending with thousands, to test safety and how well it works. Regulators, in India the Central Drugs Standard Control Organisation, review the data before approval. Monitoring continues afterwards: health systems collect reports of adverse events after immunisation, and investigate them to find out whether the vaccine caused them or the event would have happened anyway. Rare problems that are too uncommon to show up in a trial can be found this way.

Mild effects such as a sore arm, tiredness or a short fever are common and show that the immune system is responding. Serious reactions are rare, and what matters is how they compare with the harm of the disease.

In 1796 the English doctor Edward Jenner showed that exposure to cowpox protected against smallpox, and the word vaccine comes from the Latin for cow. The World Health Organization declared smallpox eradicated in 1980, the only human disease so far to be wiped out in this way. India was certified polio-free in March 2014, three years after its last reported case, after vaccination campaigns that reached more than 100 million children under five in each national round. These are among the clearest examples of what organised vaccination can do.

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