This is how we will know when a COVID-19 vaccine is ready.

Private David Lewis walked with his platoon through the snow, despite feeling bad about the flu. It was January 1976, and Lewis, 19, was stationed at Fort Dix, New Jersey, where 230 other soldiers finally fell ill. But Lewis, who collapsed 13 miles on the training walk and succumbed soon after, was the only one to die. His passing sent the United States into panic mode.

The strain collected at Fort Dix seemed similar to the one from the 1918 flu pandemic, and this connection made it great news. In the 1970s, high-risk groups were urged to get a flu shot, so the government immediately sought to adapt the vaccine against the Fort Dix strain, hoping that 80 percent of the population would take it. .

What followed was a debacle. The rapidly developed vaccine was linked to more than 500 cases of paralysis, and 25 people died from it. Shortly after the news of the Fort Dix outbreak, half the general public had expressed their intention to get vaccinated. But as the events unfolded, only 22 percent of the US population ended up receiving the vaccine by the end of the year.

Now, as COVID-19 spreads across the world and more than 140 vaccines are being worked on to protect against it, the question is: how will we know when one is good and safe enough to advise people to take it?

Although a typical vaccine can take years to take off, those designed in this pandemic advance at a rate never seen before. At least one candidate, from the modern biotech company, is heading for phase three trials in July. In May, the US government launched Operation Warp Speed, spending billions of dollars speeding up the design and testing of potential vaccines.

Some scientists are wary of deciding on the first vaccine to come to fruition. It is a delicate balancing act for public health officials to decide when a vaccine is ready for mass release to the public.

If, for example, they increase the production of a vaccine with limited effectiveness and promote it strongly, that could discourage developers from striving to bring a better one to the market. “If you accept a low-efficacy vaccine, you will probably avoid developing a more effective vaccine,” he warns. Roland Sutter, who was polio research, policy, product development and containment coordinator at the World Health Organization (WHO) in Geneva, Switzerland, until his retirement in December.

Analyzing what makes a COVID-19 vaccine good enough for mass deployment is the main challenge for scientists and policy makers in the coming months. They must also ensure adequate security controls, or risk repeating the 1976 mistakes and losing the public’s trust.

Set the goal posts

Vaccine development comes in stages, beginning with phase one trials. These clinical trials generally assess the initial safety of a drug in a relatively small number of people; sometimes about 50 participants, although the number can vary widely.

The expanded phase two trials give an idea of ​​the efficacy of the vaccine. That is often measured by testing people’s blood for antibodies or other sentinels of immunity that can neutralize the target pathogen.

The phase three trials attempt to better measure how well the vaccine protects people by increasing the scale to include thousands of participants and, generally, by comparing the protection conferred on those who are vaccinated against those who receive a placebo.

But the real test, vaccine scientists say, occurs when these preventive drugs are widely approved and administered.

“A clinical trial remains a fairly controlled environment,” says Charlie Weller, head of the vaccine program at Wellcome, a London-based biomedical research funder. People who take part in testing a vaccine may be more aware of their actions and take fewer risks of exposing them to a virus because doctors are following them. “You know you are in a clinical trial when you are in a clinical trial, and that could change your behavior,” she says. “So the real test for a vaccine is when it is implemented in a population.”

Even if they have advanced through these trials, some vaccines are simply more effective than others. (The reasons for this are not always clear. It may have to do with intrinsic factors of the virus that is being attacked, its propensity to mutate and how it spreads in the body, as well as how our immune system naturally interacts with it.)

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Vaccines known to be highly effective include inactivated polio vaccine, a three-dose cycle of inactivated polio vaccine is nearly 100 percent effective against that disease, and the measles vaccine is approximately 96 percent effective after one dose.

Other vaccines are given even though they are less likely to protect against the disease. The strains of the flu virus change from year to year, and this is part of the reason that getting the annual flu shot will only reduce your risk of getting the virus by 40 to 60 percent. The malaria vaccine, known as RTS, S, reduces severe disease by just a third, but it is still being explored as an option in the worst affected areas of the world. That’s because malaria often takes the lives of young children, and saving even a third of these young people translates into a huge gain, says Matthew Laurens, a pediatric infectious disease specialist at the Center for the Development of Vaccines (CVD) at the University of Maryland School of Medicine. in Baltimore

For the COVID-19 vaccine, the ideal candidate would be able to establish immunity in at least 70 percent of the population, including the elderly, as described in April by the World Health Organization (WHO). On June 28, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, said that he, too, would settle for a 70 to 75 percent effective vaccine.

On the other hand, the WHO says the minimum acceptable would be a COVID-19 vaccine that is 50 percent effective. Some researchers are not convinced: “Fifty percent would be terrible,” says Byram Bridle, a viral immunologist at the University of Ontario Veterinary Medicine at the University of Guelph in Canada. “For this pandemic to end, we need to achieve herd immunity,” says Bridle, and a vaccine that is only 50 percent effective falls short of that goal.

Other scientists see any vaccine as just part of a multi-faceted approach to reducing the spread of the coronavirus, along with social distancing and wearing masks. “We have to look at the full value of the vaccine for public health,” says Laurens.

Immunologists are always vigilant about the effects of new vaccines because there have been rare but notable surprises in the past. For example, the first diarrhea-causing rotavirus vaccine was withdrawn from the market in 1999 when it was associated with a rare and life-threatening slippage from one part of the intestine to another. This severe adverse event was not detected in clinical trials prior to its implementation. More recently, in 2009, the Pandemrix swine flu vaccine showed signs of a link to narcolepsy in Europe. (The vaccine was never licensed for use in the United States.)

“In a small clinical trial with the types of platforms being examined here for COVID-19, you rarely see serious reactions,” says Wayne Koff, president and CEO of the Human Vaccines Project, a public-private partnership seeking to accelerate development. of vaccines. Adults and children receive millions of doses of approved vaccines each year worldwide, and severe reactions are extremely rare.

In their phase one trials for the Modern COVID-19 vaccine, four out of 45 individuals who received the vaccine had a medically significant adverse reaction, including one man who developed a high fever and passed out. However, the researchers already knew that mRNA vaccines can sometimes overstimulate an immune system, and three of the four subjects who had these side effects were taking the highest dose in the trial, which has now been discontinued.

Problems with public recruitment

Assuming that a COVID-19 vaccine meets WHO benchmarks, including that the “benefits of the vaccine outweigh the safety risks,” an unknown part of the public will still need to convince themselves to take the vaccine.

In May, a survey of more than 1,000 people by The Associated Press-NORC Center for Public Affairs Research found that about 50 percent of respondents were confident they would take a COVID-19 vaccine when it becomes available. That’s roughly the same ratio the center found in the past when it asked about the flu shot, and it matches the results of a Pew Research Center survey conducted at the same time.

But there was a higher proportion of people who had not yet decided to get vaccinated against COVID-19 than the flu: while 18 percent of respondents had said they were not determined to get a flu shot, 31 percent said they They had not made a decision on the matter. if they would take a COVID-10 vaccine. Among those who say they could avoid a vaccine, twice as many people were concerned about the side effects of a COVID-19 vaccine as one designed to prevent influenza.

The survey also revealed a curious divergence by gender. “Women are more likely to be unsafe and on the fence,” says Jennifer Benz, deputy director of The Associated Press-NORC Center for Public Affairs Research. Their survey found that 56 percent of men said they would take the hypothetical COVID-19 vaccine, while only 43 percent of women said the same. “Women are often the ones who make health care decisions at home, so when you think about vaccinating the whole family and making health care decisions and appointments, it’s a potentially influential group,” says Benz.

The key challenge for the future, as Laurens sees it, is to explain to people how they can do their part to stop the pandemic by getting vaccinated once a suitable vaccine is available. “We have to do everything we can to educate the public about how vaccines are tested and vaccine safety profiles and what they can really do, and how they can prevent disease in a community,” he says.

Vaccination hesitation may not be the only obstacle to overcome. Weller anticipates a scenario where, at least initially, the public interest in obtaining the vaccine could exceed the amount available.

Amesh Adalja of the Johns Hopkins Center for Health Safety in Baltimore says there could be “chaotic” scenes if demand is high and deployment is not done carefully. “Just think of Black Friday and what happens when the people stand in line, “he says. , referring to the shopping day after Thanksgiving when crowds can get impatient and overwhelm stores.

Coordinators of previous immunization campaigns for other ailments are closely watching the COVID-19 vaccine development process, hoping to avoid missteps that would undermine absorption and access. “It won’t take long to discredit the vaccine in the eyes of the population,” says Sutter. “Implementation must be carefully thought out so that it does not destroy confidence in the vaccine.”