Fighting Viruses: How Do Vaccines Work?

When the body is invaded by a pathogen, such as SARS-CoV-2, the immune system typically responds by attacking it with the help of white blood cells. Several types of white blood cells exist and play different roles in the immune response. For example, B lymphocytes, or B cells, produce proteins called antibodies, which bind to the pathogen and help to neutralize it. Cytotoxic T lymphocytes, or "killer" T cells, are responsible for destroying infected cells to prevent the virus from spreading.

The human immune system has evolved to remember pathogens it has fought off in the past. If the same viruses or bacteria reinvade, the immune system can often attack them quickly.

This also explains how vaccination protects us: vaccines usually contain dead, weakened, or partial versions of the pathogens that cause a particular disease—enough to stimulate the immune response and create immunological memory but not enough to trigger harmful symptoms. In this way, vaccination allows us to develop immunity to a disease without having first been infected.

What level of immunity should we expect from vaccines?

Two main considerations associated with infection are (1) whether or not the infection will lead to disease and (2) whether or not the infection can be transmitted to others. Vaccines do not always address both.

"Sterilizing immunity" has been held up as an ideal outcome, in which immunity as a result of previous infection or vaccination completely prevents a pathogen from replicating in the body. Because the pathogen cannot replicate, it will not cause disease or be transmitted to others.

"Functional immunity" means that a person may get infected (or reinfected) by a pathogen, but their immune system will be able to respond quickly enough to keep disease from occurring or becoming severe. An infected person with functional immunity may still be able to transmit the pathogen to others, even if they show no symptoms.

Sterilizing immunity is extremely rare and may even be impossible to demonstrate. This is because it is difficult to identify people who have been infected when they do not show any symptoms. Sterilizing immunity also is not associated with viruses that attack the mucous membranes (the tissue lining body cavities such as respiratory passages), like SARS-CoV-2. Thus, as vaccines against SARS-CoV-2 are being developed, the focus has been on preventing COVID-19 rather than achieving sterilizing immunity.

Why do we get some vaccines just once and others multiple times?

Vaccine dosages and administration schedules depend, in part, on how many strains of a virus exist and on the body's immunological memory of specific pathogens.

For example, each year, researchers predict which strains of influenza will be prevalent that season and design a vaccine to target them. This is necessary because the flu virus has a relatively high mutation rate, meaning that the virus changes as it replicates itself. Some new strains are different enough from older versions that the immune system no longer recognizes them. Viruses such as HIV mutate so rapidly that vaccine development is particularly challenging.

The body's ability to remember how to fight a pathogen also may diminish over time. For the common cold coronavirus, for example, immunological memory tends to be shorter, which is why many people get colds once a year or more often. Conversely, the immune system remembers the measles, which is why the measles vaccine or infection gives lifelong protection.

While SARS-CoV-2 does not mutate as rapidly as HIV, multiple new strains have emerged, including the Delta and Omicron variants. Immunological memory for SARS-CoV-2 also seems to vary widely among individuals.

The Centers for Disease Control and Prevention (CDC) recommend that individuals get a COVID-19 vaccine primary series and boosters as soon as they are eligible. Four vaccines are authorized or approved in the U.S., including the Pfizer-BioNTech, Moderna, Johnson & Johnson's Janssen, and Novavax vaccines.

Read more about antibodies and how vaccines teach the body to make antibodies on the Caltech Science Exchange >

Read more about COVID-19 boosters on the Caltech Science Exchange >