Vaccination

Vaccination trains the immune system with a weakened, killed or partial form of a germ, so the body can fight off the real disease later. Edward Jenner showed in 1796 that cowpox protects against smallpox, and two centuries later vaccination made smallpox the first human disease to be eradicated.

What it is

Vaccination prepares the body against an infectious disease, usually before it meets the disease. The person receives a weakened, killed or partial version of the germ, or the instructions for one of its parts. The immune system responds as it would to a real infection, with far less risk than the disease itself carries, and it keeps a memory of the encounter. If the real germ arrives later, the defence starts quickly and usually stops it before it causes serious harm.

The word comes from the Latin vacca, cow. The first vaccine used cowpox, a mild disease of cattle that milkmaids caught on their hands, to protect against smallpox, one of the deadliest diseases in history. The plate is a composition: the rural setting of the 1796 experiment, with objects of the period beside it, a lancet in its case, a glass phial, a quill and the book Jenner published in 1798.

How it works

The immune system learns to recognise germs by their molecular shapes, called antigens. On a first encounter it takes days to find and multiply the right cells. Some white blood cells, the B cells, make antibodies that lock onto the germ and mark it for destruction. Others, the T cells, kill infected cells and coordinate the response. That delay is why a first infection can become severe.

After the infection is over, a population of memory cells remains, sometimes for life. A second meeting with the same antigen triggers a faster and stronger reaction. A vaccine provides that first meeting at far lower risk than the disease itself.

Cowpox worked against smallpox because the two viruses are close relatives: their antigens are similar enough that immunity to one covers the other. Later vaccines were made in other ways. Some use a living germ weakened so that it rarely causes illness, an approach Louis Pasteur pioneered; such vaccines are not given to everyone, because a person with a very weak immune system can still fall ill from them. Others use a killed germ, a purified fragment, or an inactivated toxin. The newest give cells the genetic code to make one harmless protein of the germ for a short time.

For diseases that spread from person to person, a germ can no longer pass easily once enough people in a community are immune and no longer pass it on. This herd immunity also protects people who cannot receive a particular vaccine or respond poorly to it. The share of the population needed depends on how contagious the disease is, and on how well and how long the vaccine stops transmission. Tetanus, which is caught from soil and not from other people, gives no such shared protection.

Vaccines are developed and produced under strict medical regulation and are usually given by health professionals. Like any medicine they can have side effects, which are monitored after approval.

How vaccines are made

For most of the nineteenth century the only vaccine was the one against smallpox, and the main difficulty was keeping the virus alive from one patient to the next.

Ivory points and sealed glass plates carried dried lymph from one vaccinator to the next.

Arm to arm. No one could yet grow the cowpox virus in a laboratory, so it was kept going in people. About a week after vaccination a blister formed at the site. The vaccinator opened it with a lancet and used its clear fluid, called lymph, to vaccinate the next person. To send vaccine farther, lymph was dried on small ivory points, quills or threads, or sealed between glass plates, and moistened before use. The Spanish Balmis expedition, which sailed in 1803, carried the vaccine across the Atlantic in 22 orphan boys, vaccinated two at a time during the voyage. Passing lymph from person to person could also pass on other diseases, syphilis among them.

Calf lymph. In Naples, vaccinators kept the virus going in calves from early in the century. After the method was described at a medical congress in Lyon in 1864, it spread to France and then across Europe. Calves were vaccinated with shallow scratches on a shaved patch of skin, and the pulp of the blisters was collected a few days later. In 1891 the English doctor Sydney Copeman showed that mixing this pulp with glycerine killed most of the bacteria in it over some weeks while sparing the virus. Glycerinated calf lymph, sealed in thin glass tubes, became the standard vaccine in Britain around 1900. When twentieth-century virologists examined the virus in vaccine stocks, they found it was vaccinia, a poxvirus related to cowpox but distinct from it.

Teams of the eradication programme traced every case and vaccinated the people around it.

Freeze-dried vaccine and the bifurcated needle. Liquid lymph lost its strength within a day or two in tropical heat. At the Lister Institute’s laboratories in Elstree, north of London, Leslie Collier developed a freeze-dried vaccine, protected by added peptone, that kept for months without refrigeration; he worked on it there between 1948 and 1955. During the eradication campaign that began in 1967, WHO used only freeze-dried vaccine and had batches checked by reference laboratories in Canada and the Netherlands. When the campaign started, fewer than one in ten of the vaccines in use met the standard. The bifurcated needle, developed at Wyeth Laboratories in the United States in the 1960s, is a short steel rod ending in two prongs that hold a single droplet of vaccine. The vaccinator pressed it into the skin of the upper arm about fifteen times in a small area. It used a quarter of the vaccine needed before, could be sterilised and reused, and its use could be taught in minutes.

Modern vaccines. Live attenuated vaccines use a germ weakened until it rarely causes disease: the measles virus, for instance, was weakened by growing it through many generations in cell cultures, and the BCG vaccine against tuberculosis is a weakened bacterium. Inactivated vaccines start from a germ grown in culture, viruses in eggs or cell cultures, which is then killed with a chemical such as formaldehyde; Jonas Salk’s polio vaccine of 1955 was made this way. Toxoids against tetanus and diphtheria are bacterial toxins inactivated in a similar way. Subunit vaccines contain only selected, purified parts of the germ: the recombinant hepatitis B vaccine, licensed in the United States in 1986, is a viral protein made by yeast cells that carry its gene. mRNA vaccines contain no part of the germ at all. The messenger RNA is copied by enzymes from a DNA template, purified, and wrapped in tiny particles of fat that carry it into cells.

Quality control. Production starts from a seed stock of virus, bacteria or cells kept frozen, so that the strain does not drift from batch to batch. Manufacturers test each lot for identity, sterility, purity and potency, and keep samples. In most countries a national regulator and its control laboratory review these results, and sometimes repeat the tests, before each lot may be released.

Safety. This section describes how laboratories and factories have made vaccines. Never try to prepare a vaccine yourself: home-made material can carry dangerous germs, cause serious infection and give no protection. Use only approved vaccines from released lots, given by health workers or, for the few products approved for it, exactly as prescribed.

History and evolution

Long before vaccines there was variolation, the deliberate infection of a healthy person with material from a smallpox sore. It usually caused a milder case followed by lifelong immunity, though some people died of it. The practice was old in China, India and the Ottoman Empire. Lady Mary Wortley Montagu saw it in Constantinople and in 1721 had her daughter variolated in London, which helped spread it in Britain.

Farmers in western England had long noticed that milkmaids who caught cowpox seemed spared by smallpox. The surgeon John Fewster discussed it in 1768, and in 1774 the Dorset farmer Benjamin Jesty deliberately gave cowpox to his wife and two of their children during an epidemic.

Edward Jenner, a doctor in Berkeley, Gloucestershire, turned the folk observation into an experiment. On 14 May 1796 he took material from a cowpox sore on the hand of the milkmaid Sarah Nelmes and introduced it into the arm of James Phipps. Some weeks later he exposed the boy to smallpox matter, and Phipps did not fall ill. The Royal Society did not publish his first report, so in 1798 Jenner published the case, with others, at his own expense in a short book, the Inquiry. Within a few years vaccination had spread across Europe and to the Americas.

Pasteur made vaccines by weakening the germ of the disease itself.

In the late 1870s Louis Pasteur found that a culture of chicken cholera bacteria left to age lost its power to cause disease but still protected birds. He developed vaccines against anthrax in sheep in 1881 and then against rabies. On 6 July 1885 a nine-year-old boy, Joseph Meister, who had been bitten by a rabid dog, began the treatment and survived. Accounts usually call him the first person vaccinated against rabies, although historians have found earlier attempts on patients in May and June 1885. The rabies virus usually takes weeks to reach the brain, so vaccination given soon after the bite, before any symptoms, could still prevent the disease; any suspected exposure needs immediate medical care. The twentieth century added vaccines against diphtheria, tetanus, whooping cough, tuberculosis, polio, measles and many other diseases.

In 1967 the World Health Organization launched an intensified campaign to wipe out smallpox. The last natural case occurred in Somalia in 1977, and on 8 May 1980 the World Health Assembly declared the disease eradicated. In 2020 vaccines based on messenger RNA, developed over the previous decades, were deployed against COVID-19 within a year of the virus being identified.