FOR MONTHS, a quarantine-weary, virus-ridden nation has been waiting for a COVID-19 vaccine. It’s become the endgame, the antidote to all the death and economic destruction the virus has caused. Massachusetts’s final reopening stage, referred to as the “new normal,” is predicated on having an effective treatment or vaccine. 

But experts are beginning to rein in the sky-high expectations, warning that a vaccine will not be the silver bullet that allows us to suddenly remove our masks and once again hug our friends.

“I don’t think we’re going back to normal any time soon, vaccine or no vaccine,” said Shira Doron, hospital epidemiologist at Tufts Medical Center. “It’s not going to be like everyone gets vaccinated on Monday, nobody has to wear masks Tuesday.”

Todd Ellerin, director of infectious diseases at South Shore Health, echoes that caution. “Many experts don’t think that the vaccine alone is going to get us out of the pandemic,” he said. 

Dr. Robert Redfield, director of the Centers for Disease Control and Prevention, told a Senate hearing this week that a vaccine was unlikely to be widely available until the middle of next year and, what’s more, that mask-wearing might be more effective than an immunization at stopping the virus’s spread. Hours later President Trump declared Redfield had misspoken, and Redfield appeared to partially walk back his earlier comments, tweeting that he believes a vaccine is what ultimately will “get Americans back to normal everyday life” — but saying mitigation measures like mask-wearing are our best current defense.

Much of the cautionary tone to scientists’ pronouncements stems from uncertainty over just how effective a vaccine will be and what it will mean for efforts to halt the spread of coronavirus if public health officials can’t convince enough people to get immunized. To understand those issues better, it’s helpful to review what we know and what we don’t know about the vaccine development process and the science behind it.

COVID-19, also called SARS-CoV-2, was initially transmitted from a bat to a human, which created a new, or novel, coronavirus to which human immune systems had no exposure and no immunity. 

The highly contagious disease has claimed 943,000 lives worldwide and 9,245  in Massachusetts. There is no treatment or cure. Those who have survived have done so because their bodies’ immune system was strong enough to fight back and vanquish the virus.

A vaccine attempts to help that natural process along by teaching the body’s immune system to fight a virus before it becomes infected with it. Vaccines don’t kill the virus themselves; they provide the body with a defense system in case it comes in contact with the contagion.

Some vaccines, like the measles immunization, contain the actual virus they are designed to thwart, but it has been killed or significantly weakened so the recipient doesn’t get sick. Other vaccines give you only part of the deactivated bacteria or part of a virus. The vaccine then stimulates your immune system to produce special proteins, called antibodies, that destroy the virus or block infection.

The end game of any vaccine is to reach herd immunity, the point at which enough of the population becomes resistant to the virus that the virus stops spreading and dies out. Immunity can come about two ways — by catching the disease and surviving or by taking a vaccine. Researchers at the Johns Hopkins’ Bloomberg School of Public Health have suggested that at least 70 percent of the population will need to be immune for COVID-19 to stop spreading – although estimates vary.

The US Food and Drug Administration has said it will not approve any vaccine that fails to prevent the disease or decrease its severity in at least 50 percent of people who get it. James Mayne, vice president of science and regulatory advocacy for PhRMA, the pharmaceutical company trade association, said a typical first-generation vaccine would likely be in the 70-75 percent effectiveness range. The lower the percentage, the longer it will take to reach herd immunity.

Vaccines today range widely in their effectiveness. The flu vaccine generated each year has been effective against the disease only 40 percent of the time, on average, with the numbers ranging anywhere from 10 percent to 60 percent over the last 15 years. The high variability is because the flu tends to mutate into different strains. In contrast, two doses of the measles vaccine prevent illness 97 percent of the time, according to the Centers for Disease Control and Prevention.

Ellerin, of South Shore Health, said COVID-19, as a respiratory disease, is more similar to the flu than to measles, so he expects the vaccine to act in a way more comparable to a flu vaccine. “But again, we don’t know,” Ellerin said. “That’s what the studies are going on for.”

Whatever vaccine is approved won’t be effective in building herd immunity if people don’t take it, and that is becoming a real concern. Surveys indicate half of Americans definitely plan to get a COVID-19 vaccine, but around one-third are unsure, and around one-fifth would definitely not get one. 

Although public health officials and drug companies have been stressing that developers are not cutting corners on safety and any vaccine that is released to the public will be safe, the rushed nature of developing the vaccine – and the potential politics involved with the presidential election coming up in November — have given many people pause about whether it will be safe.

Ellerin said public acceptance of a vaccine is almost as important as the vaccine itself.  “If the effectiveness is 50 percent and one-third of the country doesn’t accept it, you can do the math,” Ellerin said. 

According to the World Health Organization, there are 35 COVID-19 vaccines in clinical trials, many of them in Phase 3, the final phase of testing. Those pursuing a vaccine include pharmaceutical companies Moderna, Pfizer, Johnson & Johnson, and AstraZeneca. Several companies have ongoing Phase 3 trials in China. Russia is already distributing a vaccine, but scientists have raised questions about its safety. 

The US government has agreed to contracts with multiple drugmakers to pre-order 100 million doses of their vaccines, with options to buy millions more, assuming the vaccines receive FDA approval. 

The vaccines being tested by Moderna and Pfizer are mRNA, or messenger RNA, vaccines. Messenger RNA is injected into the body and enters the cells, where it provides instructions to produce antigens, which in turn cause the immune system to produce antibodies that remember the bad germs and stop them from replicating in the future.

Pfizer says using mRNA is beneficial because it can be developed and manufactured more quickly than traditional vaccines. But there has never been an mRNA vaccine approved in the US before. 

The method is “kind of unproven. It’s not something that people have a whole lot of experience with,” said Adam Lauring of the University of Michigan Medical School, one of the many co-investigators of the AstraZeneca trial. “This is the first time that an RNA vaccine has moved this far in the development process.”

The other leading candidates are more similar to traditional vaccines. AstraZeneca and Janssen Pharmaceutical Companies are using as their messenger viral vector platforms, which mimic the DNA in COVID-19 so the body can elicit an immune response. 

The benefit of that approach, Lauring said, is that it may stimulate a stronger immune response “and lead to more effective immunity down the road.” A disadvantage is that a vaccine using a viral vector platform would be more expensive and harder to produce on a large scale. 

A third messenger option uses an unactivated version of the protein in the COVID-19 virus — not the actual live virus, or even a dead version of it, but a protein that cannot replicate. This option tends to produce a weaker immune response and usually requires several boosters throughout a person’s life.  

Unlike the measles, mumps, and rubella vaccines, which inject someone with a weakened form of the virus, no leading vaccine candidates are currently using the actual active form of the COVID-19 virus.

Researchers say whatever vaccine candidate emerges there is no way of knowing until much later how long immunity will last for those inoculated.

Much of what is known about COVID-19 comes from studying other coronaviruses, such as the common cold, and infection with those viruses generally does not confer long-term immunity. While scientists have concluded that getting the novel coronavirus makes someone immune for some period of months, the few cases beginning to emerge of people apparently getting re-infected with COVID-19 – often after exhibiting mild or no symptoms — seem to indicate that immunity does not last forever.

“Immunity may last for a number of months but probably not lifelong, and we may be in a scenario in another year or so where you get your annual flu vaccine along with your annual COVID vaccine,” said David Hooper, chief of the infection control unit at Massachusetts General Hospital.

For some vaccinations, the antibodies weaken over time, and a booster is needed. For now, most trials are using two shots of the vaccine on participants. “There’s no way to know what you need six months from now, because we have to wait six months,” said Lindsey Baden, an infectious diseases specialist at Brigham and Women’s Hospital. The hospital is a clinical research site for a 30,000-participant trial evaluating a vaccine candidate manufactured by Cambridge-based Moderna. Baden is leading the Brigham site for the trial. 

Yet another unknown factor that will significantly limit people’s ability to return to normal is whether the vaccine stops people from transmitting the virus. It is possible that a vaccine will stop a person from getting ill — but not from carrying the virus and potentially transmitting it to someone else, even if they themselves feel fine. 

covid-19, coronavirus
Dr. Lindsey Baden, an infectious diseases specialist at Brigham and Women’s Hospital. (Photo by Len Rubenstein)

“A vaccine can reduce severity of illness or prevent actual illness but in some cases people, although they don’t get sick, can still carry the virus and shed it for a period of time,” Hooper said. “Some vaccines will do both — modify or reduce illness as well as reduce shedding. We don’t know yet about the various vaccines that are being developed as to how they will play out in that regard.” 

If the vaccine does not stop virus transmission, people will still have to continue taking preventive measures like social distancing and mask-wearing to avoid infecting people who have not been vaccinated or for whom the vaccine is ineffective.

“The vaccine could be very effective, yet you might still need to do all the things we’re doing now because you could transmit it to other people who could get very sick,” said Doron, the hospital epidemiologist at Tufts Medical Center.

Limitations on who can get a vaccine also need to be determined, including its effects on people who are older with serious conditions, women who are pregnant, and infants. 

Attention is also being paid in the ongoing clinical trials to enrolling sufficient numbers of blacks and Hispanics, as these groups have been disproportionately affected by COVID-19. Recent CDC data show that blacks, Hispanics, and American Indians are nearly three times as likely as whites to contract the virus and almost five times as likely to be hospitalized. In the Boston area, communities with high black and Hispanic populations, such as Chelsea, East Boston, and Dorchester, have seen higher infection rates than other areas during the pandemic. 

In order to determine whether there are any important race- or ethnicity-based differences in vaccine efficacy, researchers say it is crucial that clinical trials have adequate enrollment of test subjects from all backgrounds. In August, researchers wrote in a commentary piece in the New England Journal of Medicine that, despite blacks being overrepresented among COVID-19 cases and deaths, they made up just 11 percent of subjects in one small federally funded clinical trial of the drug remdesivir in treating COVID-19 patients and 20 percent of subjects in a second trial of the drug. 

Pfizer recently proposed expanding its COVID-19 trial to include more racial diversity among subjects. The Moderna test sites have also expressed interest in including the black and brown communities hard-hit by the virus. “The target population for this study are adults whose locations or circumstances put them at appreciable risk of exposure to COVID-19,” said a spokesperson for Brigham and Women’s Hospital in July.

The bottom line of all these unknowns is that even once a vaccine is available, COVID-19 may be part of our daily lives for a significant period of time.

Hooper predicted that given the time it will take people to get vaccinated and given all the questions about whether it will stop the spread, “it will be well into the winter and the spring” before people can think about dropping the other preventative measures, like distancing. Doron said it wouldn’t shock her “if we were doing it for a couple of years.” 

And all the achievements of vaccine researchers will mean little, Ellerin said, if the public isn’t willing to line up to get a shot. “Unless the vaccine has high effectiveness and the majority of Americans accept it, then it’s unlikely…that we’re going to be able to vaccinate ourselves out of this pandemic,” he said.