With a brighter future hanging on the hopes of an approved COVID-19 vaccine, is it possible to win over the minds of fearful citizens who challenge the value or safety of vaccination?

Globally, nine COVID-19 vaccines so far are being tested for safety in early phase human clinical trials.

It's a decades-old practice. With a dose injected into the arm of a healthy patient, doctors aim to prevent illness with a vaccine shot designed to trigger a person's immune system to fight serious infection without getting the disease.

This week, in fact, the U.S. frontrunner vaccine candidate, developed by Moderna, safely produced an immune response in the first eight healthy volunteers, the company announced. A large efficacy trial is planned to start in July. But if positive signals for safety and efficacy result from that trial, will that be enough to convince the public to broadly embrace a new vaccine?

"Throughout the history of vaccines there has always been a small vocal minority who don't believe vaccines work or don't trust the science," says sociologist and researcher Jennifer Reich, a professor at the University of Colorado in Denver and author of Calling the Shots: Why Parents Reject Vaccines.

Research indicates that only about 2 percent of the population say vaccines aren't necessary under any circumstance. Remarkably, a quarter to one third of American parents delay or reject the shots, not because they are anti-vaccine, but because they disapprove of the recommended timing or administration, says Reich.

Additionally, addressing distrust about how they come to market is key when talking to parents, workers or anyone targeted for a new vaccine, she says.

"When I talk to parents about why they reject vaccines for their kids, a lot of them say that they don't fully trust the process by which vaccines are regulated and tested," says Reich. "They don't trust that vaccine manufacturers -- which are for-profit companies -- are looking out for public health."

Balancing Act

Globally, nine COVID-19 vaccine candidates so far are being tested for safety in early phase human clinical trials and more than 100 are under development as scientists hustle to curtail the disease. Creating a new vaccine at a record pace requires a delicate balance of benefit and risk, says vaccinology expert Dr. Kathryn Edwards, professor of pediatrics in the division of infectious diseases at Vanderbilt University School of Medicine in Nashville, Tenn.

"We take safety very seriously," says Dr. Edwards. "We don't want something bad to happen, but we also realize that we have a terrible outbreak and we have a lot of people dying. We want to figure out how we can stop this."

In the U.S., all vaccine clinical trials have a data safety board of experts who monitor results for adverse reactions and red flags that should halt a study, notes Dr. Edwards. Any candidate that succeeds through safety and efficacy trials still requires review and approval by the Food and Drug Administration before a public launch.

Community vs. Individual

A major challenge to the deployment of a safe and effective coronavirus vaccine goes beyond the technical realm. A persistent all-out anti-vaccine sentiment has found a home and growing community on social media where conspiracies thrive. Main tenets of the movement are that vaccines are ineffective, unsafe and cause autism, despite abundant scientific evidence to the contrary.

Best-case scenario, more than one successful vaccine ascends with competing methods to achieve the same goal of preventing or lessening the severity of the COVID-19 virus.

In fact, widespread use of vaccines is considered by the U.S. Centers of Disease Control and Prevention to be one of the greatest public health achievements of the 20th Century. The World Health Organization estimates that between two million to three million deaths are avoided each year through immunization campaigns that employ vaccination to control life-threatening infectious diseases.

Most people reluctant to give their children vaccines, however, don't oppose them for everyone, but believe that they are a personal choice, says Reich.

"They think that vaccines are one strategy in personal health optimization, but they shouldn't be mandated for participation in any part of civil society," she says.

Vaccine hesitancy, like the teeter totter of social distancing acceptance, reflects the push and pull of individual versus community values, says Reich.

"A lot of people are saying, 'I take personal responsibility for my own health and I don't want a city or a county or state telling me what I should and shouldn't do,'" says Reich. "Then we also see calls for collective responsibility that says 'It's not your personal choice. This is about helping health systems function. This is about making sure vulnerable people are protected.'"

These same debates are likely to continue if a vaccine comes to market, she says.

Building Public Confidence

Reich offers solutions to address the conflict between embedded American norms and widespread embrace of an approved COVID-19 vaccine. Long-term goals: Stop blaming people when they get sick, treat illness as a community responsibility, make sick leave common for all workers, and improve public health systems.

"In the shorter run," says Reich, "health authorities and companies that might bring a vaccine to market need to work very hard to explain to the public why they should trust this vaccine and why they should use it."

The rush for a viable vaccine raises questions for consumers. To build public confidence, it's up to FDA reviewers, institutions and pharmaceutical companies to explain "what steps were skipped. What steps moved forward. How rigorous was safety testing. And to make that information clear to the public," says Reich.

Dr. Edwards says clinical trial timelines accelerated to test vaccines in humans make all the safeguards involved in the process that more compelling and important.

"There's no question we need a vaccine," she says. "But we also have to make sure that we don't harm people."

The Road Ahead

Think of manufacturing and distribution as key pitstops to keep the race for a vaccine on the road to the finish line. Both elements require substantial effort and consideration.

The speed of getting a vaccine to those who need it could hinge on the type of technology used to create it. Best-case scenario, more than one successful vaccine ascends with competing methods to achieve the same goal of preventing or lessening the severity of the COVID-19 virus.

Technological platforms fall into two basic camps, those that are proven and licensed for other viruses, and experimental approaches that may hold great promise but lack regulatory approval, says Maria Elena Bottazzi, co-director of Texas Children's Center for Vaccine Development at Baylor College of Medicine in Houston.

Moderna, for instance, employs an experimental technology called messenger RNA (mRNA) that has produced the encouraging early results in human safety trials, although some researchers criticized the company for not making the data public. The mRNA vaccine instructs cells to make copies of the key COVID-19 spike protein, with the goal of then triggering production of immune cells that can recognize and attack the virus if it ever invades the body.

"We were already seeing a lot of dissent around questions of individual freedoms and community responsibilities."

Scientists always look for ways to incorporate new technologies into drug development, says Bottazzi. On the other hand, the more basic and generic the technology, theoretically, the faster production could ramp up if a vaccine proves successful through all phases of clinical trials, she says.

"I don't want to develop a vaccine in my lab, but then I don't have anybody to hand it off to because my process is not suitable" for manufacturing or scalability, says Bottazzi.

Researchers at the Baylor lab hope to repurpose a shelved vaccine developed for the genetically similar SARS virus, with a strategy to leverage what is already known instead of "starting from scratch" to develop a COVID-19 vaccine. A recombinant protein technology similar to that used for an approved Hepatitis B vaccine lets scientists focus on identifying a suitable vaccine target without the added worry of a novel platform, says Bottazzi.

The Finish Line

If and when a COVID-19 vaccine is approved is anyone's guess. Announcing a plan to hasten vaccine development via a program dubbed Operation Warp Speed, President Trump said recently one could be available "hopefully" by the end of the year or early 2021.

Scientists urge caution, noting that safe vaccines can take 10 years or more to develop. If a rushed vaccine turns out to have safety and efficacy issues, that could add ammunition to the anti-vaccine lobby.

Emergence of a successful vaccine requires an "enormous effort" with many complex systems from the lab all the way to manufacturing enough capacity to handle a pandemic, says Bottazzi.

"At the same time, you're developing it, you're really carefully assessing its safety and ability to be effective," she says, so it's important "not to get discouraged" if it takes longer than a year or more.

To gauge if a vaccine works on a broad scale, it would have to be delivered into communities where the virus is active. There are examples in history of life-saving vaccines going first to people who could pay for them and not to those who needed them most, says Reich.

"Agencies are going to have to think about how those distribution decisions are going to be made and who is going to make them and that will go a certain way toward reassuring the public," says Reich.

A Gallup survey last year found that vaccine confidence, in general, remains high, with 86 percent of Americans believing that vaccines are safer than the diseases that they are designed to prevent. Still, recent news organization polls indicate that roughly 20 to 25 percent of Americans say they won't or are unlikely to get a COVID-19 vaccine if one becomes available.

Until the 1980s, every vaccine to hit the market was appreciated; a culture of questioning science didn't exist in the same way as today, notes Reich. Time passed and attitudes changed.

"We were already having robust arguments nationally about what counts as an expert, what's the role of the government in daily life," says Reich. "We were already seeing a lot of dissent around questions of individual freedoms and community responsibilities. COVID-19 did not create those conflicts, but they've definitely become more visible since we've moved into this pandemic."