How Do Vaccines Work, Exactly?

Credited for eliminating once-dreaded infectious diseases like smallpox, diphtheria, and polio, vaccines are heralded as one of the greatest public health achievements in modern history.

Vaccines train your immune system to recognize and fight specific disease-causing organisms known as pathogens, which include viruses and bacteria. They then leave behind memory cells that can instigate a defense should the pathogen return.

By tailoring the body's own immune defenses, vaccines provide protection against many infectious diseases, either by blocking them entirely or reducing the severity of their symptoms.

Female Doctor Injecting Syringe On Woman Shoulder In Hospital
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How the Immune System Works

The body's immune system has several lines of defense to help protect against disease and fight off infections. They are broadly classified into two parts: innate immunity and adaptive immunity.

Innate Immunity

This is the part of the immune system that you are born with. The innate immune system provides the body with its frontline defense against disease and is made of cells that are immediately activated once a pathogen appears. The cells don't recognize specific pathogens; they simply "know" a pathogen shouldn't be there and attack.

The defense system includes white blood cells known as macrophages (macro- meaning "big" and -phage meaning "eater") and dendritic cells (dendri- meaning "tree," which is fitting because of their branch-like extensions).

Dendritic cells, in particular, are responsible for presenting the pathogen to the immune system to trigger the next stage of the defense.

Adaptive Immunity

Also known as acquired immunity, the adaptive immune system responds to pathogens captured by the frontline defenders. Once presented with the pathogen, the immune system produces disease-specific proteins (called antibodies) that either attack the pathogen or recruit other cells (including B-cell or T-cell lymphocytes) to the body's defense.

Antibodies are "programmed" to recognize the attacker based specific proteins on its surface known as antigens. These antigens serve to distinguish one pathogen type from another.

Once the infection has been controlled, the immune system leaves behind memory B-cells and T-cells to act as sentinels against future attacks. Some of these are long-lasting, while others wane over time and begin to lose their memory.

How Vaccination Works

By naturally exposing the body to everyday pathogens, the body can gradually build a robust defense against a multitude of diseases. Alternatively, a body can be immunized against disease through vaccination.

Vaccination involves the introduction of a substance that the body recognizes as the pathogen, preemptively triggering a disease-specific response. In essence, the vaccine "tricks" the body into thinking it is being attacked, although the vaccine itself does not cause disease.

The vaccine may involve a dead or weakened form of the pathogen, a part of the pathogen, or a substance produced by the pathogen.

Newer technologies have enabled the creation of novel vaccines that do not involve any part of the pathogen itself but instead deliver genetic coding to cells, providing them "instructions" on how to build an antigen to spur an immune response. This new technology was used to create the Moderna and Pfizer vaccines used to fight COVID-19.

There are also therapeutic vaccines that activate the immune system to help treat certain diseases.

There are currently three therapeutic vaccines approved by the U.S. Food and Drug Administration (FDA) that can used be in the treatment of prostate cancer, invasive bladder cancer, and oncolytic melanoma. Others are currently being explored to treat viral infections like hepatitis B, hepatitis C, HIV, and human papillomavirus (HPV).

Types of Vaccines

Although the aims of all vaccinations are the same—to trigger an antigen-specific immune response—not all vaccines work in the same way.

There are five broad categories of vaccines currently in use and numerous subcategories, each with different antigenic triggers and delivery systems (vectors).

Live Attenuated Vaccines

Live attenuated vaccines use a whole, live virus or bacterium that has been weakened (attenuated) in order to make it harmless to people with healthy immune systems.

Once introduced into the body, the attenuated virus or bacteria triggers an immune response closest to that of a natural infection. Because of this, live attenuated vaccines tend to be more durable (longer-lasting) than many other types of vaccine.

Live attenuated vaccines can prevent diseases such as:

Despite the efficacy of live attenuated vaccines, they are generally not recommended for people with compromised immune systems. This includes organ transplant recipients and people with HIV, among others.

Inactivated Vaccines

Inactivated vaccines, also known as whole-killed vaccines, use whole viruses that are dead. Although the virus cannot replicate, the body will still regard it as harmful and launch an antigen-specific response.

Inactivated vaccines are used to prevent the following diseases:

Subunit Vaccines

Subunit vaccines use only a piece of the germ or a bit of protein to spark an immune response. Because they don’t use the whole virus or bacterium, side effects aren’t as common as with live vaccines. With that said, multiple doses are typically needed for the vaccine to be effective.

These also include conjugate vaccines in which the antigenic fragment is attached to a sugar molecule called a polysaccharide.

Diseases prevented by subunit vaccines include:

Toxoid Vaccines

Sometimes it’s not the bacterium or virus you need protection against but rather a toxin that the pathogen produces when it is inside the body.

Toxoid vaccines use a weakened version of the toxin—called a toxoid—to help the body learn to recognize and fight off these substances before they cause harm.

Toxoid vaccines licensed for use include those that prevent:

mRNA Vaccines

Newer mRNA vaccines involve a single strand molecule called messenger RNA (mRNA) that delivers genetic coding to cells. Within the coding are instructions on how to "build" a disease-specific antigen called a spike protein.

The mRNA is encased in a fatty lipid shell. Once the coding is delivered, the mRNA is destroyed by the cell.

There are two mRNA vaccines approved for use in 2020 to fight COVID-19:

Before COVID-19, there were no mRNA vaccines licensed for use in humans.

Vaccine Safety

Despite claims and myths to the contrary, vaccines work and, with few exceptions, are extremely safe. Throughout the development process, there are multiple tests vaccines must pass before they ever make it to your local pharmacy or healthcare provider's office.

Prior to being licensed by the FDA, manufacturers undergo stringently monitored phases of clinical research to ascertain whether their vaccine candidate is effective and safe. This typically takes years and involves no less than 15,000 trial participants.

After the vaccine is licensed, the research is reviewed by the Advisory Committee on Immunization Practices (ACIP)—a panel of public health and medical experts coordinated by the Centers for Disease Control and Prevention (CDC)—to determine whether it is appropriate to recommend the vaccine and to which groups.

Even after the vaccine is approved, it will continue to be monitored for safety and efficacy, allowing ACIP to adjust its recommendations as needed. There are three reporting systems used to track adverse vaccine reactions and channel the report to ACIP:

Herd Immunity

Vaccination may protect you as an individual, but its benefits—and ultimate success—are communal. The more people within a community who are vaccinated against an infectious disease, the fewer who are susceptible to the disease and likely to spread it.

When enough vaccinations are given, the community as a whole can be protected against the disease, even those who have not been infected. This is referred to as herd immunity.

The "tipping point" varies from one infection to the next but, generally speaking, a substantial proportion of the population must be vaccinated in order for herd immunity to develop.

With COVID-19, early studies suggest that around 70% or more of the population will need to be vaccinated in order for herd immunity to develop.

Herd immunity is what led public health officials to eradicate diseases like smallpox that used to kill millions. Even so, herd immunity is not a fixed condition. If vaccine recommendations are not adhered to, a disease can re-emerge and spread throughout the population yet again.

Such has been seen with measles, a disease declared eliminated in the United States in 2000 but one that is staging a comeback due to declines in vaccination rates among children.

Contributing to the declines are unfounded claims of harms from anti-vaccination proponents who have long asserted that vaccines are not only ineffective (or created by corporate profiteers) but may also cause conditions like autism, despite science to the contrary.

A Word From Verywell

The bulk of clinical evidence has shown that the benefits of vaccination far outweigh any potential risks.

Even so, it is important to advise your healthcare provider if you are pregnant, are immunocompromised, or have had an adverse reaction to a vaccine in the past. In some cases, a vaccine may still be given, but, in others, the vaccine may need to be substituted or avoided.

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By Robyn Correll, MPH
Robyn Correll, MPH holds a master of public health degree and has over a decade of experience working in the prevention of infectious diseases.