Here's What We Know About COVID-19 Vaccine Development and Safety

Not too long ago, the world hadn't even heard of COVID-19, much less SARS-CoV-2 (the novel coronavirus that causes the illness). Now, in the United States, there are three vaccines readily available for COVID-19.

This is remarkable, because vaccine development typically stretches over years, not months — it's a mammoth undertaking to develop, manufacture and deploy millions of doses of a vaccine.

Here, experts describe some of the challenges the COVID-19 vaccine had to overcome, and what we currently know about the three available shots.

Vaccine development is a painstaking process, and it doesn't always pay off.

A March 2013 ​PLOS One​ study looked at risks involved in vaccine research and development and found that the average vaccine takes nearly 11 years to develop and has a 6 percent chance of entering the market.

Sometimes even the most concerted efforts fall flat. An August 2013 ​Vaccine​ review traces global initiatives to develop a vaccine against human immunodeficiency virus, the virus that causes HIV/AIDS. After more than three decades, we still don't have a vaccine to prevent these infections.

So it's remarkable that there are three vaccines now authorized for emergency use in the U.S. — and clinical trials are underway for two additional ones, according to the Centers for Disease Control and Prevention (CDC).

How did we get here? Well, in May 2020, the federal government launched Operation Warp Speed, an unprecedented initiative allowing vaccine developers to perform certain tasks simultaneously, rather than sequentially. The aim was to accelerate vaccine development "without curtailing the critical steps required by sound science and regulatory standards," according to an October 2020 editorial in ​The New England Journal of Medicine​​.​

Just seven months later, in December 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the first COVID-19 vaccine.

No vaccine is 100 percent effective, according to the World Health Organization. Annual flu vaccines, for example, reduce the risk of influenza by 40 to 60 percent, per the CDC.

For COVID-19, the FDA looked for a vaccine that could prevent disease or decrease its severity in at least 50 percent of people who are vaccinated.

"That's the minimum threshold for emergency use authorization," says Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore.

The three vaccines available in the United States far exceed these minimum thresholds. Take a look at the vaccines' effectiveness, according to the Mayo Clinic:

• ​Pfizer:​ 95 percent effective at preventing COVID-19 with symptoms
• ​Moderna:​ 94 percent effective at preventing COVID-19 with symptoms
• ​Johnson & Johnson:​ 66 percent effective at preventing COVID-19 with symptoms and 85 percent effective against severe illness

Vaccine development in the U.S. involves multiple levels of safety checks, beginning with testing in cells or tissues and animals, according to The College of Physicians of Philadelphia. Only promising vaccine candidates move on to human trials.

Phase 1 trials look at safety and the immune response a vaccine candidate provokes in a small group of people. Phase 2 trials involve several hundred people. In phase 3, tens of thousands of people are randomly assigned to receive the experimental vaccine or a placebo.

Success in early human trials doesn't mean a vaccine is destined for approval. Phase 3 trials can reveal certain rare side effects that might not surface in smaller phase 1 and phase 2 studies, per The College of Physicians of Philadelphia.

To assess the risk versus benefit of a COVID-19 vaccine, the FDA intends to review at least two months of phase 3 data after trial participants have completed their final dose.

"Usually most side effects of vaccines happen in the first four to six weeks," says Hana El Sahly, MD, associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, a phase 3 testing site for Moderna's vaccine.

Once safety data is reviewed and the FDA gives the nod, "we're pretty sure that there aren't going to be adverse events popping up left and right," says Arthur L. Caplan, PhD, professor of bioethics at the New York University Grossman School of Medicine in New York City.

Also, it's in companies' best interest to assure their vaccines are safe. "If they put out a vaccine and it gets into safety trouble, they're going to lose a lot of money and they're going to lose a lot of investors," he tells LIVESTRONG.com.

The vaccines available in the United States are all considered safe, according to the CDC. Hundreds of millions of doses have been administered. And for most people, COVID-19 vaccine side effects are minor and short-lived.

There are two exceptions: With the J&J/Janssen vaccine, some people have experienced anaphylaxis (a severe allergic reaction) or thrombosis with thrombocytopenia syndrome (TTS), according to the CDC. But these side effects are quite rare: For instance, TTS — a type of blood clot — has occurred in seven per 1 million vaccinated women between 18 and 49 years old, notes the CDC.

While the Johnson & Johnson vaccine is a one-shot deal, the Pfizer and Moderna vaccines require two doses, and so do several other COVID-19 vaccine candidates. After the first shot, a second is given a few weeks later.

The problem is that some people may not bother getting a second shot or presume they're done after the first dose. In the history of vaccines, "anything that's been a two-shot vaccine has turned out to be a pain in the neck. People don't comply," Caplan pointed out during a media briefing on the topic.

Some people might sit out vaccination altogether.

As of June 2021, 42 percent of the United States is fully vaccinated, and more than half of the country has received at least one dose, according to the Mayo Clinic.

The goal, of course, is to get everyone vaccinated. To that end, a wide range of incentives — from state-level lotteries with big payoffs to free french fries, donuts or beer with proof of vaccination — are available.

And efforts are underway to make getting vaccinated simple and convenient, such as providing free child care, extending pharmacy hours and encouraging employers to offer on-site vaccination clinics (as many do in the lead-up to flu season), NPR reports.

How long will a COVID-19 vaccine last? It's a question vaccine researchers — people like Kirsten Lyke, MD, professor of medicine at the University of Maryland School of Medicine in Baltimore — are trying to answer.

She's been on the front lines of clinical trials of two different vaccines. Each uses messenger RNA (mRNA), an approach she likens to delivering a bit of computer code into a cell, instructing it to make spike protein (the type found on the surface of the novel coronavirus). When the body's immune system encounters the protein, it makes antibodies. It's teaching your immune system to recognize COVID, she says, so that when you encounter the virus, your immune system ramps up quickly.

"We know that it can make good protein and we know it can make good neutralizing antibodies, but we don't know how long that'll last," Dr. Lyke says.

What if a vaccine imparts immunity, but it only lasts a few months? People would need booster shots, creating additional expense and distribution hassles, Caplan points out. We might even learn that the vaccine lasts for a shorter period of time in certain populations. It may fade faster in older adults, for example. "You might have to re-vaccinate them every three months," he says.

Here's what we currently know about available vaccines: Trials indicate the Pfizer vaccine is effective for at least six months, per Pfizer. The Moderna vaccine is known to be effective for a similar amount of time, according to correspondence in ​The New England Journal of Medicine​. Further studies are needed to know if the vaccines are effective beyond six months, and when (if at all) a booster shot might be required.

After several months of vaccine shortages and logistical snarls around finding and making appointments, getting vaccinated is now a simple and frequently same-day process. At CVS Pharmacy, for instance, you can simply walk in and get the shot.

Enter your zip code on Vaccines.gov to find a nearby appointment for the dose of your choice.

Vaccines are available in the U.S. at no cost, according to the CDC. Health insurance is not required to get vaccinated, nor does immigration status matter.

​— Additional reporting by Jaime Osnato​