How Vaccines Work: The Science, Main Types and History Explained

Vaccines work by showing the immune system a harmless version of a pathogen's antigen — the part of a bacterium or virus that the body recognizes as foreign — according to the World Health Organization's European regional office. This exposure trains the immune system without causing the disease itself.

The immune mechanism

When the immune system meets an antigen, white blood cells called B-lymphocytes produce antibodies shaped to bind to that specific antigen, WHO Europe explains. These antibodies can block the pathogen directly or mark it for destruction by other immune cells such as phagocytes.

The immune system also keeps 'memory' cells after this encounter. WHO Europe notes that an unvaccinated person's first natural infection can take seven to twelve days before the body mounts an effective defense — a delay during which severe illness or death can occur. Vaccination allows the memory response to form in advance, so a later encounter with the real pathogen triggers a faster, stronger reaction. WHO Europe adds that immunity from this memory can last for years, decades or a lifetime, though it stresses that routine vaccines are 'very effective' but 'none is 100% effective,' which is why some vaccines require multiple doses.

Active versus passive immunity

The CDC's Pink Book, the agency's reference manual on vaccine-preventable diseases, distinguishes two routes to immunity. Passive immunity comes from antibodies made by another source, such as a fetus receiving maternal antibodies during pregnancy; it gives immediate but temporary protection that fades over weeks to months. Active immunity develops when a person's own immune system responds — either to a natural infection or to a vaccine — and, because of immunologic memory, it typically lasts for years or a lifetime.

Main vaccine types

The CDC Pink Book groups most traditional vaccines into two broad categories. Live-attenuated vaccines contain a weakened form of the virus or bacterium that still replicates in the body, producing an immune response the Pink Book describes as 'virtually identical' to a natural infection; these typically need only one injected dose. Inactivated vaccines cannot replicate and come in several subtypes: whole-cell vaccines use a killed pathogen (examples include polio, hepatitis A and rabies vaccines); subunit vaccines use only protective pieces of the organism (influenza, pneumococcal); toxoid vaccines use an inactivated bacterial toxin (diphtheria, tetanus); conjugate vaccines chemically attach a polysaccharide to a protein to improve response in young children; and recombinant vaccines use DNA technology to produce specific antigens (hepatitis B, HPV).

Two newer platforms were used widely during the COVID-19 pandemic. The CDC's COVID-19 vaccine guidance explains that mRNA vaccines, used in the Pfizer-BioNTech and Moderna shots, deliver lab-made genetic instructions that direct muscle cells to briefly produce a harmless piece of the virus's spike protein; the immune system then reacts to that displayed protein before the mRNA itself is broken down and cleared by the body. Protein subunit vaccines, such as Novavax's, instead inject the spike protein piece directly along with an adjuvant that strengthens the immune response.

Origins: from variolation to Jenner's vaccine

The practice of deliberately exposing people to a mild form of a disease to prevent a severe case predates modern vaccination by centuries. WHO's history of vaccination resource states that variolation — using material from smallpox sores to induce a milder infection — may date back as early as 200 BCE, with documented techniques in China by the mid-1500s and in India by the 18th century. Lady Mary Wortley Montagu introduced the practice to Europe in 1721 after observing it in the Ottoman Empire, and in the American colonies the technique, known through enslaved West Africans, was publicized by Cotton Mather during a 1721 Massachusetts outbreak.

The modern vaccine emerged in May 1796, when English physician Edward Jenner inoculated eight-year-old James Phipps with material from a cowpox sore on the hand of milkmaid Sarah Nelmes, according to WHO's history page. Two months later, in July 1796, Jenner deliberately exposed Phipps to smallpox matter; Phipps did not develop the disease, making him, in WHO's account, 'the first person to be vaccinated against smallpox.' By 1801 further testing had confirmed the method's effectiveness.

From mandatory vaccination to global eradication

According to WHO, mandatory smallpox vaccination began in Britain and parts of the United States in the 1840s and 1850s. In the 1950s, a heat-stable, freeze-dried version of the vaccine removed the need for constant refrigeration, aiding wider distribution. WHO called for global smallpox eradication in 1958, and the Intensified Smallpox Eradication Programme began in 1967 using a freeze-dried vaccine developed in the Soviet Union.

The disease was eliminated region by region: from South America in 1971, from Asia in 1975 and from Africa in 1977, WHO's timeline states. The World Health Organization officially declared smallpox eradicated in 1980 — the only human disease eliminated through vaccination to date, per WHO's account.