As hopes rise for pandemic’s close, some are preparing for never-ending COVID

Scores of companies, many in Massachusetts, gear up to fight the virus ‘in perpetuity’

Vaccinations are continuing in Boston at the Harvard Street Neighborhood Health Center clinic at the Prince Hall Grand Lodge. People may need booster shots in the future.Craig F. Walker/Globe Staff

A pandemic-weary public is dreaming of Memorial Day barbecues, summer nights at Fenway Park, and putting the long-running curse of COVID-19 behind us.

But in the medical and biopharma worlds, many are eyeing a more daunting prospect: coronavirus as a never-ending threat.

Governments and private investors who once shunned vaccines as an unprofitable pharmaceutical backwater are pouring billions into venerable drug giants and upstart biotechs, including some in Massachusetts, seeking to develop longer-lasting vaccines.

The makers of three US-authorized vaccines — Moderna, Pfizer-BioNTech, and Johnson & Johnson — are testing COVID-19 booster shots to protect against more-contagious variants first detected in the United Kingdom, Brazil, and South Africa.

And hundreds of potential treatments and diagnostics are in the works as public health leaders brace for testing and tracing regimens far into the future.

“We believe [COVID-19] and its variants will be circulating through the human population in perpetuity,” said Tillman Gerngross, chief executive of Adagio Therapeutics, a Waltham biotech startup that last week said it raised $336 million to develop antibody drugs for coronavirus infections. “It may become less deadly, but it’s going to be around.”

The growing conviction that scientists will be waging a permanent war on the virus, its variants, and similar pathogens yet to emerge stems partly from a recognition that bats and other animals harbor viruses that can be transmitted to humans and spread quickly around the planet. COVID-19 is widely believed to be such a “zoonotic disease,” and there’s no reason to think that the pattern won’t repeat itself.

Meanwhile, the glacial pace of COVID-19 vaccinations in much of the world, the likelihood that immunity wanes over time, and the rise of more-resistant variants may leave millions vulnerable. Although makers of the three vaccines deployed in the United States hope they protect against the variants that have emerged so far, other mutations to the shape-shifting virus could produce more threatening forms.

“Did I expect [variants] would become a problem so quickly?” said Andrea Carfi, head of infectious disease research at Cambridge-based Moderna. “Maybe not.” But, he said, “we are very well positioned” with groundbreaking messenger RNA molecules that can easily be reprogrammed to disarm new strains.

Moderna is pursuing three options to strengthen COVID defenses: a third dose of its current vaccine, a vaccine tailored for the B.1.351 variant first seen in South Africa, and a dose that combines the two. The South African variant caused a sixfold reduction in the effectiveness of virus-disabling antibodies, though even at that reduced level the vaccine is still widely thought to be protective.

Some epidemiologists have begun talking about a post-pandemic landscape in which the coronavirus that causes COVID-19, called SARS-CoV-2, is “endemic,” meaning it continues to circulate in pockets of the world, but not cause the deaths, illnesses, and lockdowns endured for more than a year. Think of the measles, flu, and HIV. In that scenario, vaccinated people in Massachusetts and nationwide would coexist with outbreaks but likely be able to return to relatively normal lives.

If the US vaccine campaign proceeds at the current rate — lately about 3 million doses a day — the country will achieve “some element of normalcy” this summer, suggested Dr. Dan Barouch, head of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, which licensed technology for the one-shot J&J vaccine.

But, he warned, the global pandemic will not be over because most countries lag behind the United States. Only about 10 nations — prosperous countries such as Israel, United Arab Emirates, and Chile — have vaccinated substantial shares of their populations against COVID-19. And the emergence of variants underscores that a wildfire in one part of the globe is a threat to the entire world.

There’s also the risk that something can go wrong with the US vaccination program, as Barouch knows all too well. The rollout of J&J’s vaccine, which provided robust protection against severe disease and death in clinical trials, was temporarily halted in the United States this month so health officials could investigate extremely rare but potentially lethal blood clots reported in a small number of recipients. US health officials lifted the pause Friday shortly after an expert panel recommended that vaccinations resume for all adults and that the label warn people to get medical attention if they develop worrisome symptoms.

More than 218 million doses of the Pfizer, Moderna, and J&J vaccines have been administered in the United States so far, creating a kind of split screen America between the vaccinated and those who are not: Infections have plunged for older folks, the majority of whom are vaccinated, while cases are exploding in the unvaccinated young, allowing more-transmissible variants to gain traction. Because the variants travel quickly, the virus poses an ongoing risk of reinfection and fresh outbreaks if vaccine immunity wanes.

“It’s going to continue at some level,” said Dr. Paul Offit, a pediatrician at the Children’s Hospital of Philadelphia, who sits on the Food and Drug Administration advisory committee that recommended clearing the Pfizer, Moderna, and J&J vaccines for emergency use. “I can’t imagine this virus won’t be with us for decades.”

That prospect is keeping scientists busy in labs from Cambridge’s Kendall Square to the San Francisco Bay Area, from Zurich to Jerusalem. Researchers are working on more than 850 treatments and vaccines targeting COVID-19, according to a data tracker at the Washington, D.C.-based Biotechnology Innovation Organization, a trade group.

About 100 companies and hospitals with operations in Massachusetts were developing vaccines, drugs, and diagnostic tests, according to a survey last summer by the Massachusetts Biotechnology Council. Some of those efforts have likely fizzled out, while new ones have started, said the trade group, which plans to update the list soon.

Many companies are still developing COVID-19 vaccines even though the front-runners have already reached the market. Translate Bio in Lexington, in partnership with Sanofi Pasteur, the vaccines division of the French pharma giant Sanofi, is working on a vaccine based on the same messenger RNA technology as the Pfizer and Moderna vaccines.

“We believe there’s room for a third, and maybe a fourth or a fifth,” said chief executive Ron Renaud. “You’ve got these variants popping up pretty frequently now.”

Renaud said he envisions coronavirus vaccines or boosters being administered yearly, like flu vaccines. That likely health necessity could also yield a healthy business.

Companies are also experimenting with new vaccine approaches. California biotech Gritstone is working on a vaccine that employs “broadly neutralizing antibodies” to defeat multiple variants. About 60 of its researchers, based in Cambridge, are also trying another strategy, developing a model for deploying T cells to stop the virus.

Andrew Allen, the cofounder and president of Gritstone, calls COVID “a foe that we’re going to have to contend with for the foreseeable future.”

Makers of the three authorized vaccines in the United States are pressing ahead as well. J&J is testing whether a second dose of its vaccine boosts immunity at clinical trial sites located where variants are widespread, including South Africa, Brazil, and the United Kingdom, Barouch said. Pfizer and its German partner BioNTech are also testing a third dose of their first-to-market vaccine against B.1.351 and other strains.

Pfizer chief executive Albert Bourla told CNBC recently that people will likely need the booster six to 12 months after their COVID-19 vaccination shots “and then from there, there will be an annual revaccination.”

Alongside the “preemptive” strategies pursued by drug makers, systems engineers envision a new infrastructure that can rapidly deliver tests for pathogens, store test processing instrumentation in bunkers near population centers, and efficiently distribute vaccines and treatments globally.

“We need to have these systems ready to go in the same way we do for missiles or aircraft carriers,” said Michael Mina, assistant professor of epidemiology at Harvard’s T.H. Chan School of Public Health, who’s developing a global immune observatory using blood samples to track pathogens.

With relatively few people immunized in South America, Africa, and even large swaths of Europe and Asia, the potential for them to spawn virulent variants that could quickly spread worldwide is being closely watched.

“If we let the virus run wild in Brazil, in India, in other parts of the world, we’re tempting fate,” said Dr. Ashish Jha, dean of the Brown University School of Public Health. “We may see a variant emerge that could defeat the vaccine.”

Vast amounts of resources are pouring into the field to make sure that doesn’t happen. Earlier this month the Biden administration said it would allocate $1.7 billion from its COVID-19 relief package to track “new and potentially dangerous strains” of coronavirus. An international coalition of governments, businesses, and philanthropies has raised $8 billion to hasten new treatments, vaccines, and diagnostics and make sure they are available throughout the world.

Biotech investors are ponying up billions more, some of it aimed at creating what Noubar Afeyan, founder of Flagship Pioneering in Cambridge, has called a “global pathogen shield” — a vaccine manufacturing and distribution infrastructure that can mobilize rapidly against emerging threats.

Afeyan, whose firm created and bankrolled high-flying Moderna, said the campaign against the new COVID-19 strains may be the first proving ground for that strategy. “Going after variants is something we have to get a lot better at,” he said.

Not everyone agrees a permanent war against COVID-19 is inevitable. Some scientists say that will depend on several unanswered questions: How long will it take to vaccinate enough of the world’s nearly 8 billion people to curb the virus’s spread? How long will vaccines protect fully inoculated people? And can the race to vaccinate the world be completed before even more troublesome variants emerge?

Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, said much of the planet could by immunized by the end of next year.

His optimism stems, he said, from the fact that the virus mutations cropping up so far have remained within a range where vaccinations can still be effective. “That says you can design a booster shot that can cover these variants,” he said. “So we can vaccinate our way out of this.”

But set against that optimism, most nations are now battling widespread hesitancy that threatens to leave pockets of their populations unvaccinated. Even if large-scale vaccination occurs, scientists fear protection could wane over time.

Tellingly, some who once suggested that vaccinating 70 to 90 percent of the population could carry us to “herd immunity” — where COVID-19 disappears because the virus can find few hosts — now are backing away from any predictions.

“Rather than concentrating on an elusive number, let’s get as many people vaccinated as quickly as we possibly can,” Dr. Anthony Fauci, the top US infectious disease specialist, said at a recent White House coronavirus briefing.