How vaccines work: Infectious disease experts available for interviews

When cases of polio appeared in New York around 1916, public health officials struggled to contain the outbreak through quarantines, which began in June and lasted until November.

In 1952 alone in the U.S. polio infected nearly 60,000 children, paralyzed thousands and more than 3,000 children died.

The first polio vaccine was announced in 1955 and by 1979 polio was eliminated in the U.S.

Diseases that once burned through populations are now increasingly rare because of vaccines.

An estimated 103 million cases of childhood diseases were prevented between 1924 and 2010 in the U.S. through vaccinating against diseases such as measles, mumps, rubella (MMR), diphtheria and pertussis.

“What all vaccines have in common is that they trick the immune system into thinking you are infected,” said Marietta Vazquez, MD, Pediatric Infectious Disease, Yale New Haven Hospital. “Your body responds by creating protective factors so that when you or your child encounter the real pathogen, your body knows how to fight it. Sometimes people experience side effects after a vaccination, like fevers or aches, which tell us your body is responding to the vaccine.”

Dr. Vazquez emphasizes that vaccines work on two levels; protecting the individual and protecting a population. Pathogens, which include disease causing agents such as viruses and bacteria and are sometimes called germs, need susceptible people in order to survive and spread. “No vaccine is 100 percent effective, but your illness, should you get sick, will be much milder than if you had not gotten vaccinated,” said Dr. Vazquez.

All approved vaccines are extensively tested and highly regulated. Different pathogens behave differently necessitating an array of vaccine types outlined below.

Live attenuated vaccine

In a live attenuated vaccine the live pathogen has been modified into a weaker version.

These vaccines elicit a strong immune response because the virus is replicating in the body. The strain is too weak to get most people sick. The MMR and varicella vaccines fall into this category.

Some vaccines that were originally live attenuated are no longer widely used in this form. For example, the oral polio vaccine is only used where wild polio still circulates and in places where administering injections broadly is not feasible. In 1 in 2.7 million doses someone will get polio from the oral live attenuated version of this vaccine. These infections are milder than a natural infection would be. This is considered an adverse event and is reported to a vaccine surveillance program called the Vaccine Adverse Event Reporting System.

“There are systems monitoring vaccine adverse events worldwide,” said Saad Omer MBBS PhD, director, Yale Institute for Global Health, “With these surveillance systems, we continue to rule out rarer and rarer side effects.”

In the United States we use a whole-inactivated vaccine for polio which cannot transmit the polio virus.

Whole inactivated vaccine

This type of vaccine includes the whole pathogen, but it has been deactivated in a laboratory. The body develops a strong immune response, but people will likely need booster shots to maintain immunity. There is no live virus replicating in the body after these vaccines.

The flu vaccine falls into this category, along with hepatitis A and rabies.

Toxoid vaccine

Toxoid vaccines are an inactivated version of a bacterial toxin. Some bacteria don’t cause illness directly, but rather produce a harmful toxin in the human body. A toxoid vaccine gives the recipient an inactivated toxin that stimulates a protective immune response.

The diphtheria and tetanus vaccines fall into this category.

Diphtheria was a childhood disease called the “strangling angel.” It was known for creating a pseudo membrane on the roof of the mouth and eventually cut off air flow to many of its victims. The U.S. recorded 206,000 cases of diphtheria in 1921, resulting in 15,520 deaths. The current U.S. childhood immunization schedule for diphtheria includes five diphtheria toxoid immunizations before age six, plus one booster dose for adolescents in what is called the DTaP vaccine. The CDC reported 56 cases of diphtheria in the U.S. in 2019.

Conjugate vaccine

Some bacteria have evolved to evade our immune system. They are coated with sugars, called bacterial capsular polysaccharides, instead of proteins like our immune system is used to seeing and fighting. Conjugate vaccines are designed to induce a robust immune response against these sugars by attaching them to proteins so the immune system can recognize the polysaccharides and make antibodies against the bacteria.

The vaccine for haemophilus influenzae type b, which is a bacteria responsible for some neonatal infections, falls in this category.

Protein subunit vaccine

Protein subunit vaccines include only the part of the pathogen the immune system needs to see — like its protein, sugar, or capsid (a casing around the pathogen) to stimulate an immune response.

The first subunit vaccine to be approved for use in humans in the U.S. is the hepatitis B vaccine, which was approved in 1981.

mRNA vaccine

Viruses are DNA, which is genetic material, surrounded by protein. To target a virus, the immune system just needs to recognize the protein on the outside of the virus – not necessarily the DNA inside of it. Like most vaccines, mRNA vaccines exploit this principle.

mRNA are instructions for cells. In the case of the mRNA COVID-19 vaccines, the instructions tell immune cells to make spike proteins that resemble the ones attached to the COVID-19 virus, specifically SARS-CoV-2. Once this protein is made, the immune system can mount a response to these spike proteins, memorize how to attack them, effectively preparing the body to fight a COVID-19 exposure.

While a COVID-19 vaccine may be the first licensed mRNA vaccine in the U.S. for use in humans, researchers have been working with mRNA for decades. These types of vaccines have been studied for flu, zika and rabies.

Yale New Haven Hospital partnered with Yale School of Medicine on Phase 3 of the first COVID-19 vaccine candidate approved by the U.S. Food and Drug Administration (FDA) for Emergency Use Authorization. This vaccine is an mRNA vaccine.

Notes on COVID-19 vaccines

“Funding public health takes resources, but not funding it is much more costly,” said Dr. Omer. “The COVID-19 vaccine rollout underscores how important it is even during non-pandemic times to have systems and platforms in place that can help ensure rapid access to life saving vaccines and treatments as well as solid communications plans.”

Dr. Vazquez encourages people to bring questions about any type of vaccine to their health care providers.

“By sharing specific concerns we can have productive conversations that don’t have any agenda other than to discuss evidence-based information,” said Dr. Vazquez.

Learn more about COVID-19 Vaccine Information on Distribution and Answers to Other Common Questions.

This article has been reviewed by:
Saad B. Omer, MBBS, PhD, director, Yale Institute for Global Health; associate dean (Global Health Research). Dr. Omer’s research on vaccination rates, exemptions, and outbreaks of vaccine-preventable diseases has been widely covered in medical journals. On March 5, 2019, he testified at a US Senate hearing on vaccines, stating that preventing the next potential resurgence of measles will require a broad-based federal response to improve vaccine access.
Marietta Vazquez, MD, Pediatric Infectious Disease, Yale New Haven Hospital. Dr. Vazquez treats a variety of infections, from the commonly seen cases of ear infections, pneumonia, and respiratory infections to more rare and complicated conditions including meningitis, brain and bone infections. Dr. Vazquez practices both infectious diseases and general pediatrics at the Yale School of Medicine and directs the Yale Clinic for Hispanic Children (YCHiC) for families with children up to 1 year old. Dr. Vazquez’s research focuses on vaccines, and she is also involved in global health studies. She is a professor of Pediatrics at Yale School of Medicine and is vice chair of diversity, equity and inclusion for the Department of Pediatrics.