Initially, the experiment was a bust. The patients Wang tested had antibodies only against the older version of SARS. But as a number of Covid variants began spreading early this year, he decided to test the patients again. By this point, many of the Singaporean SARS survivors had also been vaccinated against Covid, providing a rare set of immune systems that had been exposed to proteins from these related coronaviruses.
relates to The Hunt for a Single Shot to Defeat Omicron and All Coronaviruses
Wang at his office in Singapore.PHOTOGRAPHER: JULIANA TAN FOR BLOOMBERG BUSINESSWEEK
What Wang found astonished him. After getting the Covid shot, the SARS patients had developed something akin to super-antibodies, which blocked both SARS viruses and a multitude of other coronaviruses. All eight patients had antibodies that, in test-tube experiments, neutralized five different bat and pangolin coronavirus strains that had never infected humans. The results, published in the New England Journal of Medicine in August, offered one of the strongest bodies of evidence that a universal coronavirus vaccine is possible.
The need is growing—as public health officials know all too well, three new coronavirus diseases have emerged in just 20 years: first SARS, then MERS in 2012, and now Covid. At his 13th-floor lab a few kilometers from Singapore’s central business district, Wang is working on a prototype vaccine that could generate the same type of wide-ranging immune response he saw in the Covid-vaccinated SARS survivors. His regimen combines a first shot containing the Covid spike protein with a second shot containing a hybrid SARS protein. If it works—Wang says experiments in mice are promising—the vaccine could be deployed in the event of a Covid-26 or a SARS-3.
“We want something that is broadly protective, so that when the next one jumps from animals to humans, we already have a vaccine in hand,” says Melanie Saville, head of vaccine research and development at the Coalition for Epidemic Preparedness Innovations, a global nonprofit based in Oslo. CEPI plans to spend $200 million to develop broad-acting coronavirus vaccines over the next five years. One of its first grants under the program was awarded in November to Israel’s MigVax Ltd., a crowdfunded startup working on a “variant-proof” Covid vaccine in tablet form.
Important questions remain unanswered, such as which parts of the virus to target, which technology works best, and how broad-acting the shots should be. Pfizer Inc., Moderna Inc., and many other major Covid vaccine companies aren’t investing heavily so far, instead waiting as the academic research plays out. Mikael Dolsten, chief scientific officer of Pfizer—which is researching an omicron booster and is developing ones for the beta and delta variants with its mRNA vaccine partner, BioNTech SE—says that, given that existing vaccines work and that mRNA shots can be quickly updated, it could be “a dangerous game” to switch tracks to a pancoronavirus shot. “We are following it, but it’s more of an academic approach at the moment,” Dolsten says. “I would say stay with what works.” He posits, too, that waning effectiveness of vaccines over time could turn out to be a bigger problem than variants, something universal shots wouldn’t necessarily solve.
Stéphane Bancel, chief executive officer of Moderna, which is also developing mRNA boosters against the beta, delta, and omicron variants, calls universal vaccines “a good idea” and says he’d be happy to strike partnerships to develop them when viable options emerge. But he cautions that researchers have been working on universal flu vaccines for years without a breakthrough.
It’s true that scientists have long dreamed of developing a vaccine that would eliminate the need for an annual flu shot. There’s been no breakthrough, though several trials are under way. The difficulty has been the pace of mutation: Influenza evolves rapidly. The speed at which coronaviruses evolve is intensely debated, but the case for broad-acting shots is nonetheless compelling, given the promising results from early attempts, the increasing frequency with which coronaviruses have been crossing over from other species, and the staggering human and financial costs of Covid. “It would be crazy not to do something,” says Pamela Bjorkman, a structural biologist at the California Institute of Technology who’s working on a universal vaccine. “For the world to act like ‘Wow, we have solved this’ is really shortsighted.”
The history of flu vaccines offers an object lesson. Early shots were pioneered in the 1940s by University of Michigan virologist Thomas Francis with help from the U.S. Army, which was worried about an epidemic ravaging troops in crowded barracks. Francis and his protégé, Jonas Salk, grew the vaccine in fertilized chicken eggs, a method still in wide use today. The first shots showed strong efficacy in many studies. One influenza B shot given to troops receiving specialized training at the university in 1945 proved 88% effective, not far from the 90%-plus efficacy reported for the mRNA Covid shots. The researchers quickly realized that strains could evolve from year to year, resulting in a mismatch between vaccine and virus. But they were optimistic it would be manageable. “The outlook for increasingly broad and effective prophylactic immunization against the range of influenza viruses is extremely promising,” Francis concluded in a 1953 publication.
The early flu shots contained two viral strains, then three in the 1970s, and finally four in the past decade. Research focused heavily on attacking the most abundant protein found on a virus’s surface, hemagglutinin, with flu shots selected each year based on their ability to generate antibodies against it. But for much of the vaccine’s history, doctors couldn’t accurately measure how shots were performing in the real world. After modern viral load tests—the same kind of PCR tests used to definitively diagnose Covid today—started being used in the 1990s, enabling researchers to study real-world flu vaccine performance more carefully, it slowly became clear that the results varied widely and topped out at middling. Since 2004, even as more of the U.S. population has been getting vaccinated annually in keeping with expanded government recommendations, the shot’s real-world effectiveness has ranged between only 10% and 60%, according to the Centers for Disease Control and Prevention. Most years, it’s around 40% to 50%.
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