How Vaccines Work

Jenner was operating on the now widely accepted principle that once a person catches a certain disease, he or she is immune to it for the rest of their life. For example, once you've had the chickenpox, it's extremely unlikely that you'll ever catch it again. This is because your body, when exposed again, will recognize the disease and fight it off. The beauty of vaccines is that they help the body develop disease-fighting abilities without making you sick. Vaccines accomplish this amazing feat by tricking the body into believing it already has the full-blown disease. Here are the steps in this process, known as the "immune response":

It's very important to note that when the actual disease infects a person, the antigens multiply thousands and thousands of times until a raging infection is underway. The vaccine provides just enough of these antigens for the body to recognize them and complete the immune response process, therefore protecting them from exposure to the disease in the future.

The procedure for developing a vaccine takes many years and even more money, often hundreds of millions of dollars. Therefore, according to John Bradley, M.D., member of the committee on infectious diseases of the American Academy of Pediatrics (AAP), developing vaccines are prioritized in this order:

Additionally, vaccines are studied and produced by companies, so the return on investment must be significant in order to justify the large expense. Vaccines are currently in development to prevent malaria. The malaria vaccine has been slighted in the past because the financial return was not worth the investment the industry had to make, according to Dr. Bradley. It's also extremely difficult to develop a malaria vaccine because of the complex nature of the parasite. As of April 2020 there is no commercially available malaria vaccine, although it continues to be studied in hopes that eventually this will change [source: World Health Organization].

Another reason that vaccines can be tricky to produce is that some viruses mutate so quickly that traditional vaccines are ineffective. A prime example is HIV (human immunodeficiency virus). Despite these hurdles, there is currently a tremendous movement to develop a vaccine to fight HIV and AIDS. The COVID-19 pandemic has resulted in millions of people being infected with the virus and hundreds of thousands of deaths worldwide. The race is on to develop a vaccine, with currently more than 100 projects going on in 2020. So far no one knows when one will be available. It's estimated that even with compressing vaccine trials, a vaccine may not be ready before 2021, which shows how difficult it is to bring a safe vaccine to the public.

Vaccines are usually given via a hypodermic injection, but some are given through the mouth or nose. There are two main groups of vaccines: live-attenuated vaccines and inactivated vaccines.

Live-attenuated vaccines: Live-attenuated basically means alive, but very weak. These vaccines are made when the virus is weakened to such a level that it reproduces only about 20 times in the body. By comparison, natural viruses reproduce thousands of times. When the vaccine is made, the virus or bacteria is weakened in a laboratory to the point where it's still alive and able to reproduce but can't cause serious illness. Its presence is enough to cause the immune system to produce antibodies to fight off the particular disease in the future.

"Live-attenuated vaccines can cause very mild illness in a small proportion of people," says John Bradley, M.D. "However, these side effects are usually very mild and limited to a low-grade fever or runny nose." Dr. Bradley also notes that about 5 to 10 percent of children who receive the varicella (chickenpox) vaccine develop a few pox spots, but it's nothing compared to the full-blown illness.

To weaken the virus before innoculation, scientists must isolate it through a specimen from an infected person. They then grow the virus in a test tube. They "pass" the virus into a second test tube, then a third, a fourth and so on. Scientists perform this "passage" many times – the measles virus was passed 77 times! The virus is periodically taken out of the test tube to see if it has mutated. Eventually, the virus gets so used to living in the comfortable test-tube environment that it loses its capacity to produce illness in humans. These passages are performed in a very controlled environment in exactly the same way each time. This discovery was considered the "hallelujah" of vaccine development, according to William Schaffner, M.D., professor and chair of the Department of Preventive Medicine at Vanderbilt University School of Medicine.

Examples of live-attenuated vaccines are MMR (measles, mumps and rubella combination vaccine), varicella and the intranasal form of influenza.

Inactivated vaccines: When inactivated vaccines are made, the bacteria is completely killed using a chemical, usually formaldehyde. Dead pieces of disease-causing microorganisms (usually bacteria) are put into the vaccine. Because the antigens are dead, the strength of these vaccines tends to wear off over time, resulting in less long-lasting immunity. So, multiple doses of inactivated vaccines are usually necessary to provide the best protection. The benefit of inactivated vaccines is that there is zero chance of developing any disease-related symptoms – allergic reactions are possible but extremely rare.

Examples of inactivated vaccines are hepatitis A, hepatitis B, poliovirus, Haemophilus influenzae type b (Hib), meningococcal, pneumococcal and the injected form of influenza.

Why are some vaccines live and some dead?

"The bottom line is that the decision is entirely driven by the science," says Dr. Schaffner. "If scientists can make a killed vaccine that is effective, that is what they will do. It's all about trial and error." Most viral diseases, he says, require live-attenuated vaccines, but the vast majority of bacterial illnesses are prevented with inactivated vaccines. There are some exceptions to this rule, though. For example:

So, what, exactly, are the ingredients of a vaccine? Other than the antigen, a couple of things have to be included in the vaccine in order for it to be effective. The requirements vary depending on the specific vaccine, but the gist is the same. There will be ingredients included to keep the vaccine safe such as aluminum salts, antibiotics, and formaldehyde.

The vaccine has to be stable because it leaves the manufacturing plant, gets bounced around on trucks and so forth. Sometimes small chemicals are added to act as stabilizers so that the vaccine material remains potent. These chemicals are thoroughly regulated by the Food and Drug Administration (FDA) to ensure their safety and are usually present only in trace amounts.

In multidose vials, a disinfectant is required. This is so that each time a dose is removed, any foreign matter that intrudes is killed instantly. Traditionally, Thimerosal has been the most popular among scientists. However, the industry has largely abandoned its use because of concerns that the chemical causes adverse reactions. In fact, multidose vials are being phased out in favor of single-dose vials, even though these are more expensive. Thimerosal is currently present only in trace amounts in the influenza vaccine, but that will be a thing of the past in a few years. "We would like to put the controversy behind us," says Dr. Schaffner. "None of us associated with vaccines believe there is merit to that belief, but we are going the extra hundred miles to reassure parents."

The process of creating, testing and producing a vaccine in mass quantities can take many years from start to finish because the industry is highly regulated. Before scientists even begin to formulate a vaccine, researchers have to study the particular virus or bacteria. Basically, they have to isolate it in a laboratory setting and figure out how it causes the disease. Then they develop the vaccine as either a live-attenuated or inactivated vaccine, depending on the type of virus or bacteria.

Once they have a good grip on that, researchers study the best ways to protect people from the disease using the vaccine they have developed. They figure out the best dosage amounts, whether or not one shot is good enough, or if more is necessary. They also estimate how long protection from the vaccine lasts to determine if booster shots will be necessary. Most of this early research is conducted in laboratories in an academic setting and is paid for by foundation or government grants.

Once the vaccine has been developed, the testing process is conducted over four phases and a period of many years. This testing is funded by pharmaceutical companies and can rack up hundreds of millions of dollars in bills.

The first studies usually test the vaccine on about a hundred healthy adults who are at low risk for complications. The researchers want to find out if the vaccine is safe and if it induces the immune response necessary to fight off disease. If this phase isn't successful, the vaccine is taken back to the drawing board or abandoned.

If Phase 1 is successful, the vaccine moves to the second phase of study, involving a few hundred people from the vaccine's intended group. For example, the chickenpox vaccine was probably tested on children at this phase because they are the target audience. The vaccine is tested on several hundred people to again ensure its safety. Researchers also want to verify that the vaccine causes the desired immune response consistently.

The third phase can take many years and studies anywhere from a thousand to tens of thousands of people in various lifestyles and geographic locations. Researchers want to make sure that the vaccine works on people of all types and in all environments. The FDA reviews all of the data and the study methodology. If everything is satisfactory, the FDA deems the vaccine safe, but then it must be approved by a board of vaccine experts who advise the CDC. The experts then distribute their recommendations about dosage, who should receive the vaccine, when they should receive it, etc.

Even after the vaccine has been distributed, it still requires many more years of study to make sure that no unforeseen side effects occur. The CDC monitors the vaccine and possible side effects very closely in four types of study:

Who should get vaccinated – and when? For what? Read on for a thorough explanation.

Babies and young children have always been a major focus of the vaccine movement. However, public health experts want to make sure that adolescents, adults and the elderly stay up to ­date on their immunizations.

"Vaccines are not just for babies anymore," says Angie Matthiessen, MSW, of Immunize Georgia and Children's Healthcare of Atlanta. "Many adolescent and adult vaccines are now in place, often to protect the very young and elderly."

Visit your doctor regularly to stay up to date on vaccinations. Many insurance plans cover the majority of vaccine-related charges because they're considered necessary preventative measures. Often, walk-in clinics provide vaccinations for a nominal fee.

Some physicians are able to give vaccines to children as part of the Vaccines for Children Program free or at very little cost. Children under 18 are eligible if they're at least one of the following:

School requirements for vaccinations vary from state to state. The requirements for each state can be accessed here.

Travel requirements are pretty limited. International Health Regulations mandate that the yellow fever vaccination is necessary for travel to certain countries in tropical South America and sub-Saharan Africa. The Saudi Arabian government requires that visitors receive the meningococcal vaccination if visiting during the Hajj. Other than that, the CDC recommends that all international travelers be up to date on regular vaccinations. Whether or not travelers need extra vaccines depends on factors such as the destination country, season and whether rural areas will be visited. The CDC provides a comprehensive destination list for travelers to review here.

On the next page, we'll give you a full list of infant vaccinations in the U.S.

Vaccines are most effective at preventing disease when the recommended schedule is followed. Over the next three sections, we'll go over the schedules for infants, children and adults in the U.S.

Infants receive the lion's share of vaccines. First, babies have very immature immune systems and are at greater risk of complications and death if exposed to disease. Second, experts believe that a strict vaccine schedule from birth on helps to ensure that these diseases don't pop back up and cause large-scale epidemics. It is recommended that babies from birth to 15 months receive the following vaccines (see the CDC vaccination schedule for exact ages):

HepB: Hepatitis B is transmitted through blood transfusions, direct contact with infected bodily fluids, sexual contact, body piercing and tattoos. According to the CDC, of the children who acquire lifelong hepatitis B, 25 percent die of liver disease in adulthood.

DTaP: Combination vaccine that prevents three diseases (diphtheria, tetanus and pertussis) in one shot.

Hib: The Haemophilus influenzae type b (Hib) vaccine protects against meningitis (infection of the covering around the brain and spinal cord). Meningitis once caused terrible complications in survivors, including mental retardation, deafness and seizures.

IPV (inactivated poliovirus): Spread through direct contact with fecal matter, polio once caused 13,000 to 20,000 cases annually in the United States alone. Paralytic polio left many victims relegated to wheelchairs, crutches and leg braces.

PCV (Pneumococcus): Causes complications such as meningitis, pneumonia, blood infection (sepsis) and brain damage. It is spread through coughing and sneezing and is especially dangerous to the elderly.

MMR (Measles, mumps and rubella): Another combination vaccine. These three diseases are spread through coughing and sneezing.

Varicella (chickenpox): Chickenpox used to cause approximately 4 million cases, 11,000 hospitalizations and 100 deaths per year before the vaccine became available in 1995. Complications are worse for teens and adults and include lung and brain damage and death. The trademark itchy rash usually covers the entire body.

HepA: Hepatitis A is usually spread via contaminated food and water, often in situations with bad food preparation habits and in developing countries. It can cause very low energy for as long as a year and liver failure, joint pain and kidney and blood disorders.

Rota (rotavirus): A common disease that infects almost all children in the United States before school age. The disease usually causes fever, nausea and diarrhea. In less developed countries it causes more than 500,000 deaths annually.

Influenza (the flu): The disease, which is spread through coughing, sneezing and other direct contact, can cause complications like brain swelling, pneumonia and death in severe cases. The Spanish flu pandemic of 1918 caused 675,000 deaths in the United States and 50 million deaths across the globe, according to the CDC. Because the flu virus changes each year, this vaccine is given annually.

"There is absolutely no chance that you can catch the flu from the flu shot," says Dr. Bradley. Sometimes the flu vaccine is mismatched to the particular virus so the protection isn't there, or these people were already coming down with the flu when they got the vaccine.

After all these vaccines, babies get a few years to rest before their next round of immunizations. Next we'll talk about childhood vaccinations.

Early childhood: From age 18 months to 6 years, children receive subsequent vaccinations of HepB, DTaP, IPV, MMR and varicella. This is to ensure maximum protection against the diseases.

Later childhood/adolescence: After age 6, children don't have too many shots to worry about until adolescence. Around age 11 they should get the DTaP vaccine to protect against tetanus, diphtheria and pertussis because the vaccine they received as an infant has worn off. The following are also recommended at age 11 to 12:

Young people also need a booster for pertussis, better known to many as whooping cough. Most infants receive the vaccine, but it wears off by adolescence. Many teens and parents aren't aware that middle-school-age children should receive a booster vaccine to protect themselves and others.

While teens and adults can catch and suffer from the disease, it's often fatal to the very young and very old. Babies receive the vaccine in three doses, so they aren't protected completely from the disease for many months. According to the CDC, most infant deaths from pertussis occur in babies under 3 months old. The elderly and people with poor immune systems are also at elevated risk because their immune systems are much weaker.

"The point is that if you are around an elderly person or a baby you really need to have this shot," says Joyce Allers, R.N., of Children's Healthcare of Atlanta. "We as a society have to protect our more fragile members. They [people whose children are not up-to-date on vaccines] are taking their child out in public where they may be exposing a grandfather recovering from cancer to a potentially deadly disease."

Pertussis is often misdiagnosed because it shares symptoms with other common respiratory ailments. Symptoms include a severe cough that can last eight weeks or more, momentary loss of consciousness, low-grade fever and a runny nose.

Adults have to get shots, too. Find out about them on the next page.

Adult (18-65): Adults should be revaccinated for any of the already-mentioned diseases if there's evidence of waning immunity. For example, when a woman becomes pregnant, her doctor usually runs tests to make sure that she's still immune to German measles. Also, not all adults have received every vaccine, either because they weren't available when they were children, or they were never immunized in the first place. Further, some vaccines have a limited life span. DTaP, TD (tetanus and diphtheria) and flu are common vaccinations or re-vaccinations for adults.

Elderly (over 65): Adults over age 65 are at an increased risk of complications from disease, simply because their immune systems aren't what they used to be. Pertussis, pneumococcus and the flu pose extra threats to this age group. The elderly should make sure that their vaccinations are up-to-date because some may have worn off over time. The following is also recommended:

High-risk groups: These are children and adults who don't have the best immune systems. These are usually people with compromised immune systems from diseases such as cancer. The schedule for these patients is largely controlled by their particular specialist and should be maintained because the disease can be harsher on them than others [source: CDC].

Vaccines aren't just for humans. Pets are lining up for shots to prevent illness and death as part of their annual check-ups. Experts agree that vaccines have protected millions of animals over the years. Pet owners should talk to a veterinarian about which vaccines are necessary (core) and which are optional (non-core), because there is some variation depending on where you live and whether or not your pet goes outdoors.

Some debate is heating up between people who think that animals need yearly revaccinations and those that think it's unnecessary. Unfortunately, there's not enough evidence to prove beyond a reasonable doubt that immunity lasts more than a year.

Complete recommended vaccine schedules for dogs, cats and other animals are available here.

There can be confusion and misunderstanding about vaccines. On the next page we'll debunk some of the myths you might have heard.

Here are some of the most well-known myths about vaccines as well as the reality.

MYTH: Vaccines cause autism.

TRUTH: This myth gained popularity when children were diagnosed with autism around the time that they received the MMR vaccine (around 18 months of age), according to Joyce Allers, RN, with Children's Healthcare of Atlanta. (There was also a now-discredited study published in Lancet in 1998 alleging a connection.) At the time, the mercury-containing preservative Thimerosal was being put in some vaccines – although not the MMR vaccine – to keep bacteria from growing, so many people connected that to autism. However, there appears to be no link between previous use of Thimerosal and autism. Thimerosal was completely removed from all infant vaccines in the United States in 2001, yet autism rates continue to increase. "Study after study has shown that there is no link between vaccines and autism," says Angie Matthiessen with Children's Healthcare of Atlanta.

Thimerosal is currently present only in minute amounts in the influenza vaccine. There are also Thimerosal-free influenza vaccines.

MYTH: Vaccines aren't necessary anymore because all the diseases are gone anyway.

TRUTH: According to the CDC, if we stopped vaccinating, many diseases that are largely unknown would come back with a vengeance. The only vaccine-preventable disease that's been completely wiped out is smallpox. "These diseases are coming into our country, into our schools and into our workplace," says Matthiessen. "Don't believe that your child is 100 percent protected because the disease isn't currently in the United States. International travel and adoption are two of the ways that dangerous diseases make their way into the country."

Measles, which the U.S. considered wiped out in 2000 has returned. There were 1,282 cases of measles in the U.S. in 2019. The CDC attributed the outbreak to "an increase in the number of travelers who get measles abroad and bring it into the U.S., and a spread of measles in U.S. communities with pockets of unvaccinated people." Some Americans have become resistant to immunizing their children, which has contributed to the spread of some childhood diseases that were once seldom seen.

MYTH: Babies are too fragile to get so many shots.

TRUTH: "A lot of young parents are worried about giving their babies so many shots, thinking that they will overwhelm their immune system," says Allers. "I tell them that as human beings we are exposed to disease all the time, like at the mall and church, so we can't overwhelm their systems." According to the Children's Hospital of Philadelphia's Vaccine Education Center, diseases often occur in very young infants, so the best way to prevent them is to give vaccines as soon as possible after birth. "We have a wonderful history of eliminating disease, but what worries us is all the good progress we've made is going to be diminished by families choosing their own vaccination schedule or choosing not to vaccinate at all," Allers says.

MYTH: A live vaccine can give me the disease it's supposed to prevent.

TRUTH: As we've discussed, live vaccines can cause extremely mild symptoms. However, experts agree that they are very minor and much better than coming down with the full-blown disease.

For more information on vaccines and related topics, check out the links on the next page.