Vaccine FAQs: How Are Vaccines Developed, and How Do They Work?

Vaccines are a pillar of good public health. And as the world continues to fight COVID-19, there’s much anticipation for the continued rollout of safe and effective vaccines to help get the pandemic under control.

Vaccines save millions of lives each year from deadly diseases caused by viruses or bacteria. “Diseases such as smallpox and polio that were killers a century or two ago are now barely blips in our conscience,” notes pulmonologist Daniel Culver, DO.

They’re crucial to fighting infectious diseases — yet there’s still a lot of misinformation floating around about vaccines. Here’s what you should know about how they’re developed, how they work and the science behind COVID-19 vaccines.

How do vaccines work?

You encounter thousands of germs every day. While your immune system can fight most of them on its own, vaccines help it fight the disease-causing ones (pathogens) it can’t handle.

Vaccines familiarize your immune system — which makes antibodies to defend your body against harmful invaders — with a certain pathogen so that it will know what to do if you become infected with that pathogen in the future.

There are several different ways that vaccines can achieve this triggering of the immune system, Dr. Culver says. They contain either:

• A weakened (attenuated) form of a pathogen.
• An inactivated form of a pathogen.
• Certain parts of the pathogen, such as its proteins.
• A weakened toxin made by the pathogen.

Vaccines may also contain other ingredients such as adjuvants, which help boost your body’s immune response to the vaccine, and stabilizers, which keep the active ingredients working after the vaccine is made.

It’s important to note that vaccines don’t make you sick with the pathogen they’re designed to protect you from. Rather, they give your immune system a practice run at taking out a weaker, inactivated or partial version of the pathogen.

Very rarely, vaccines can cause severe physical reactions, but usually they’re mild — like some soreness where the vaccine was injected, a low-grade fever or achiness. “This really means the immune system is sitting up and taking notice of the vaccine,” Dr. Culver says.

In some cases, like with the MMR vaccine, you need more than one dose of a vaccine to build strong immunity. With others, like the tetanus vaccine, your immunity wears off over time and you need occasional “booster” vaccines. In the case of the flu vaccine, the main targets of the immune response shift slightly from year to year, depending on which flu virus strains are circulating most that year, so you need a vaccine every year.

How vaccines protect you (and others)

Most vaccines won’t prevent you from becoming infected with a certain pathogen. Rather, they allow your body to stop the infection before you get sick, or they prevent you from becoming seriously sick when you get infected.

For example, the flu shot reduces your risk of getting the flu by 40% to 60%, according to the CDC. That might not seem like a lot, but studies also estimate that getting the flu vaccine makes you 82% less likely to be admitted to an intensive care unit with flu-related illness than someone who isn’t vaccinated.

This helps you, and it also helps those around you, including people in your community who can’t be vaccinated because of serious allergies or a medical condition that weakens their immune system. Pathogens can spread quickly from person to person. When a large number of people in a community are vaccinated, the pathogen can’t spread as easily.

“If that number gets high enough, we’ll have what’s called herd immunity, where there aren’t enough people in a community who can spread it in a significant way,” Dr. Culver says.

What vaccines do we need?

In the U.S., the Centers for Disease Control and Prevention recommends that children be vaccinated against:

• Hepatitis B.
• Diphtheria, tetanus and pertussis (whooping cough).
• Haemophilus influenza type b.
• Polio.
• Pneumococcal bacteria.
• Rotavirus.
• Influenza.
• Chickenpox.
• Hepatitis A.
• Measles, mumps and rubella.
• Meningococcal disease.
• Human pappilomavirus.

There are also some vaccines you should get later in life, including tetanus boosters. The CDC’s recommended immunization schedules for children and adults are available on its website.

How are vaccines developed?

Like medicines, vaccines go through a long process of research, development and approval before they’re made available to the public. “The usual timeline for developing a vaccine is certainly more than 10 years and probably closer to 15 or 20 years,” Dr. Culver says.

Exploratory and pre-clinical research

It starts in a lab, where scientists work to understand a pathogen and figure out how they could trigger the immune system to produce antibodies against it. When they identify a substance they think could work (an antigen), they start by testing it in cell cultures and then animals.

In the U.S., the sponsor of a new vaccine must submit an application to the Food and Drug Administration before they can begin testing it in humans.

Clinical trials

Vaccine developers must complete a three-phase clinical trial process to show that their product is safe and effective before it can be approved. This includes:

• Phase 1: A small number of people (usually healthy people) receive the vaccine. The purpose of a phase 1 trial is to see whether, or how, the vaccine generates an immune response in humans and if it causes any potentially dangerous side effects.
• Phase 2: The vaccine is given to more people (at least several hundred) of various ages and levels of health. Phase 2 studies allow researchers to better evaluate how safe and effective the vaccine is and learn what the ideal dosage is.
• Phase 3: Hundreds or thousands of people receive the vaccine, and its safety and effectiveness are monitored for a longer period of time.

Regulatory review

In the U.S., the FDA must approve a new vaccine before it can be made available to the public. “Regulators look at all the safety and effectiveness data collected from lab studies and clinical trials and then make a determination on whether or not this will be a product that actually will be helpful for the population,” Dr. Culver explains.

Once it’s approved, the vaccine then must be manufactured and distributed, which is a complex and time-consuming process. But not a lot of vaccines actually make it this far.

“Vaccines are very hard to develop,” Dr. Culver says. “Sometimes they may look very good in early-phase trials but then may not turn out to effective in phase 3 trials.”

If a vaccine is approved, regulators and drug companies continue to monitor its safety and effectiveness as more people take it.

COVID-19 vaccines

Because of the global crisis at hand, work on vaccines to protect against COVID-19 has happened at lightning speed. “Biopharmaceutical companies and the academic industry — with a lot of support from organizations and governments around the world — are all working in partnership to try to move this very fast,” Dr. Culver says.

That doesn’t necessarily mean they’ve skipped important steps along the way, though. “The process of developing these vaccines is being done very rigorously,” he says. “Many of these steps have just been collapsed so that they’re overlapping.”

For example, manufacturing of Pfizer’s and Moderna’s vaccines began before the FDA authorized them for emergency use, so that they could be distributed as soon as possible.

Several other COVID-19 vaccines are in development or testing. Different groups are taking different approaches to triggering an immune response. Some are using an inactivated, weakened or partial version of the coronavirus that causes COVID-19 to trigger an immune response. But Dr. Culver points out that many are using newer, gene-based approaches that deliver genetic code to our cells instructing them to make a specific protein contained in the coronavirus. This, in turn, triggers the immune system to make antibodies against that protein.

Vaccine developers are hoping to get that genetic code into our cells in three ways:

• Viral vector vaccines, which use a common cold-causing virus to deliver the genetic code to our cells.
• DNA vaccines, which contain small, circular pieces of DNA called plasmid.
• RNA vaccines, which contain RNA carried in fatty molecules that can pass easily into cells. (Both of the vaccines that have been authorized for emergency use in the U.S. fall into this category.)

“We’re going to see which one of these is most effective – and I certainly hope that more than one is effective,” Dr. Culver says.

On Feb. 27, the FDA issued Emergency Use Authorization (EUA) for Johnson & Johnson’s single-dose COVID-19 vaccine that was developed by Janssen Pharmaceuticals. The company has since started shipping its COVID-19 vaccine and expects to deliver enough single-shot vaccines to vaccinate more than 20 million Americans by the end of March.

Will a vaccine end the pandemic?

While effective vaccines are a key part of the strategy for squashing COVID-19, it’s important to remember that they aren’t an “off” switch for the pandemic.

“Vaccines are part of the solution for getting control over this, but I think it’s highly unlikely that a vaccine will be 100% effective and will be used by enough of the population regularly enough to completely eliminate this virus from our world,” Dr. Culver says.

“I think we’ll need to have a strategy that includes several things, including vaccination, continued social distancing measures, rigorous testing and contact tracing — and if we can combine all of those elements, we can get back to something that’s very close to a normal life.”

In the meantime, the best way to protect yourself and those around you is by doing the things you’re probably tired of hearing about: good social distancing, wearing a mask in the appropriate setting, hand-washing and staying out of crowds.

“It’s important to remember that the extent to which we can open the economy and go back to school and do the sorts of things we all enjoy as part of life really depends on personal responsibility from each of us,” Dr. Culver says.