How Vaccines Work to Create Immunity
In nature, when a pathogen such as a bacteria or virus enters the body, it will reproduce, causing an infection and illness. The body can usually respond to an infection and slowly recover—that is, the body’s natural immune system recognizes the pathogen and fights it off. After the body recovers, some immune cells will remember the pathogen and be prepared to fight it off if it sees it again. This is called infection-derived immunity, or immunity that comes through being infected or sick.
Vaccines act similarly, but instead work to protect the body from future infections without getting infected with the pathogen first. Vaccines prime the body to respond to a future infection by introducing a non-disease-causing version of the pathogen to the immune system. The immune system recognizes this and prompts the body’s immune cells to remember the pathogen so that if the body later encounters the actual pathogen, it can respond quickly before the virus or bacteria has a chance to divide rapidly and cause illness. In short, vaccines offer us immunity without the risks that come from being infected with a disease, like severe illness, hospitalization, or even death. This is called vaccine-derived immunity.
The First Vaccines
The concept of vaccination, also referred to as inoculation, was used as early as the year 1,000 CE in China, where substance from smallpox scabs was placed in the nostrils or on the skin of healthy individuals to prevent smallpox infection. In 1796, Edward Jenner demonstrated the concept of vaccination against smallpox by inoculating a boy with cowpox (cowpox is a virus in the same family as smallpox). On dairy farms, when cattle would get cowpox, animals would experience mild illness and workers would get sores on their body where they encountered the virus. Jenner took substance from a cowpox sore on one worker and inoculated an 8-year-old boy with it. The boy became ill but recovered. Later, Jenner exposed the boy to smallpox and he was immune – he didn’t become infected or sick. This is one of the best recorded examples of early immunization. Jenner’s method was studied and researched for the next 200 years and eventually, thanks to vaccination, smallpox was eradicated across the globe, becoming the only human-infecting disease to be wiped out of existence. Through the middle of the 20th century, vaccine research moved forward at rapid speed, leading to vaccines for polio, mumps, measles, diphtheria, tuberculosis, tetanus and other diseases. Scientists are now studying and using new techniques in vaccine research, like the messenger RNA (mRNA) technology used for COVID-19 vaccines.
Vaccination has come a long a way since the late 1700s. Today, vaccines are intensely monitored for safety and efficacy, and there are many kinds of vaccines. Different vaccine technologies work best for protecting against different pathogens. Individuals may be better suited for certain vaccine technologies, depending on their age and immune system. Some vaccines are more practical than others due to logistics, such as access to vaccine refrigerators. When developing vaccines, scientists consider these factors to determine the best technology to use.
So, what are the different kinds of vaccines, and how do they work?
One of the earliest methods developed for vaccinations was through live attenuation. Live-attenuated vaccines contain the pathogen (bacteria or virus) the vaccine is used to protect against, but in a weakened (attenuated) form. The bacteria or virus included in the vaccine is genetically modified, so it cannot cause disease, but it still appears like the actual pathogen to the immune system. These vaccines are very effective, but may not be suitable for individuals who have compromised immune systems.
Examples of live-attenuated vaccines include: measles, mumps, and rubella (MMR) vaccine, varicella (chickenpox) vaccine, yellow fever vaccine, rotavirus vaccine, smallpox vaccine
Inactivated vaccines contain a killed or modified version of the pathogen, which allows the immune system to recognize the pathogen in whole (as opposed to just recognizing a part of the pathogen); the killed or modified pathogen is unable to replicate and cause disease. As opposed to live-attenuated vaccines, multiple doses are often needed for inactivated vaccines to create a strong enough immune response.
Examples of inactivated vaccines include: polio vaccine, influenza vaccine, hepatitis A vaccine, rabies vaccine
Subunit vaccines contain just a piece of the pathogen they are protecting against, rather than the whole bacteria or virus. Subunit vaccines may have different names based on the type of subunit used. For example, polysaccharide vaccines contain a sugar that is found on the pathogen’s surface, and conjugate vaccines contain the polysaccharide component attached to another protein antigen. The immune response generated from subunit vaccines is specific to a part of the bacteria or virus delivered by the vaccine rather than the entire pathogen. Subunit vaccines typically require adjuvants, or substances that increase a vaccine’s efficacy. Subunit vaccines work especially well in children under two and are acceptable for most individuals with compromised immune systems or long-term health issues. Boosters (additional doses of the vaccine) of subunit vaccines are often needed to guarantee ongoing protection.
Examples of sub-unit vaccines include: Haemophilus influenzae type B (Hib) vaccine (conjugate), pneumococcal vaccine (polysaccharide or conjugate), shingles vaccine (recombinant protein), hepatitis B vaccine (recombinant protein), acellular pertussis vaccine, MenACWY vaccine (conjugate)
Like subunit vaccines, toxoid vaccines contain a weakened version of a bacterial toxin called a toxoid that a pathogen produces. Toxoid vaccines prime the immune system to specifically respond to that toxoid. These vaccines are specifically used to prevent certain bacterial infections and typically require booster shots.
Examples of toxoid vaccines include: tetanus vaccine, diphtheria vaccine
Viral vector vaccines
Viral vector vaccines take advantage of the body’s natural viral system to deliver genetic material into the body’s cells. These vaccines use a modified version of a different virus as a “vector,” or carrier, for genetic material. The body’s cells process the material and create a protein, which the body then recognizes as a threat and triggers the immune system to produce antibodies against it. This method elicits a strong immune response. Viruses that have been used as vectors in vaccines include influenza, measles virus, and adenovirus.
Examples of viral vector vaccines include: Ebola vaccine, COVID-19 vaccine (AstraZeneca and Johnson & Johnson), also used in studies for Zika, flu, and HIV vaccines
Nucleic Acid Vaccines
Messenger RNA (mRNA) vaccines
mRNA vaccines are very quick to develop, making them a great technology to use for vaccines that need to be modified quickly due to emerging variants, or mass-produced to serve a large population. Like viral vector vaccines, mRNA vaccines create proteins in order to trigger the body’s immune response. First, the vaccine delivers a messenger RNA transcript into the body’s cells; the cells then use the RNA transcript as instructions to produce a certain protein. These proteins are typically the same as the proteins found on a pathogen’s surface. The body recognizes the protein as a threat and primes the immune system to respond to the protein if it ever sees it again on a pathogen. The field of mRNA vaccines is rapidly growing, and these kinds of vaccines are being produced to protect against a variety of vaccines.
Examples of mRNA vaccines include: COVID-19 vaccine (Pfizer-BioNTech and Moderna)
DNA vaccines deliver a piece of genetic material (DNA) in a plasmid (or lipid carrier) into the body. The DNA codes for a specific protein on the pathogen and prompts the body to mount an immune response to that protein, and therefore the pathogen if it enters the body in the future. DNA vaccines can be quickly developed to respond to an outbreak.
Vaccine science is always evolving, and scientists are continually finding new ways to use vaccine technology to protect against diseases. Thanks to vaccines, we’ve seen the number of cases of vaccine-preventable diseases drop drastically worldwide; diseases like polio, measles, tetanus and chickenpox have been eliminated (or not actively spreading or circulating) in many areas across the globe. To continue to see low rates of these diseases and potentially one day eradicate them for good, we need to continue to prioritize routine vaccination. After all, vaccines have been one of the greatest, most impactful contributions to global health in recent history.