For quite a few of the people interviewed for this article, the speed with which Covid vaccines were developed was truly unexpected. Ran Balicer, director of Israel’s Clalit Research Institute, encapsulated that view: “Vaccine(s) ready, tested, and launched in under a year.”

For others, the surprise was how effective the vaccines were. “I was on the Pfizer DSMB” — the data and safety monitoring board, a group of independent experts who oversee a clinical trial — “and was one of the people that unblinded that study the first time and saw the 95% efficacy. Basically it just brought tears to my eyes,” said Kathryn Edwards, a professor of pediatrics and vice-chair for clinical research at Vanderbilt University.

Still others were stunned at how many vaccine development attempts were successful. Hatchett is now the CEO of the Coalition for Epidemic Preparedness Innovations (CEPI), an organization whose mission is to spur development of vaccines for diseases that can trigger dangerous epidemics or pandemics, vaccines for which there isn’t a market — until suddenly there is. He thought there would be a Covid vaccine within 12 to 18 months of the start of the pandemic; in fact, the first vaccines were ready in 11 months. But historically, only about 1 in 10 vaccine projects succeeds. Hatchett figured that would be the case here too.

Instead, Covid vaccine after Covid vaccine worked. Old-school inactivated vaccines, the foundation of China’s vaccination effort. New messenger RNA vaccines like Pfizer’s and Moderna’s. Recombinant protein vaccines like the one made by Novavax. Viral-vectored vaccines, like the AstraZeneca and Johnson & Johnson jabs. True, there were a few failures, but far fewer than anyone anticipated. Hatchett puts it down to investments in vaccinology.

“I think we should draw encouragement from that, in that if we make a concerted effort to be ready for other threats, I think we have powerful tools that tilt the balance in our favor,” Hatchett said. “It just showed how much progress we had made before Covid arrived.”

Perhaps the biggest vaccines surprise, though, was the speed at which gobsmacking amounts of vaccine were produced. Billions and billions of doses in the first year of production alone.

Hatchett has spent nearly two decades working on pandemic preparedness. The past three years have held few surprises for him. But he marveled at what he called “this truly miraculous scaling of production.”

“A lot of cumulative advances that we had never seen mobilized all at the same time, for the same purpose, suddenly showing their power,” he said. “That was a big surprise.”

Not all the vaccine surprises were positive
For all the wondrous surprises related to the vaccines, some were disappointing.

They have been potent protectors against the worst of Covid, cutting hospitalizations and deaths dramatically. But protection against infection declines rapidly over a course of a few months — at least with the mRNA vaccines. “Going from 95% to negligible in terms of transmission in the time window in which that has occurred — that’s pretty dramatic,” said Bieniasz, the Rockefeller University virologist.

Vaccine hesitancy and rejection has been a growing problem for years, but before the pandemic, the scale of the problem in the United States was still relatively small. The vast majority of parents vaccinated their kids against childhood diseases.

And in the early days of the vaccine rollout, when supplies were tight, people jostled and misrepresented themselves and called in favors to try to get to the front of the line faster. But anti-vax forces mobilized to attack the new vaccines. Rumors flew that they attacked testicles and altered fertility. A surprising level of distrust took
hold. As vaccine supplies began to swell, demand began to evaporate.

Messonnier knew all about vaccine hesitancy. But even she was taken aback by how quickly “must have” turned to “meh.”

“I expected people to see vaccines as they did at the end of 2020, as being the thing that was going to save us, the thing that was going to get life back to normal. And that moment when folks felt that way just passed so quickly,” said Messonnier, who is now dean of the Gillings School of Global Public Health at the University of North Carolina.

Claire Hannan, too, was surprised by how fleeting the keen-to-get-vaccine moment was. Hannan is the executive director of the Association of Immunization Managers, which represents leaders of state, local, and territorial immunization programs — the people who oversee the efforts to turn vaccines in vials into vaccinations in arms.

The last couple of years have been extraordinarily busy for Hannan and her members.

“The initial surge in demand and the craziness and the logistics and all of the challenges and the lack of funding and lack of staffing — expected all of that,” she said. “It was what came after that that surprised me.’’

Another vaccine-related issue Hannan wasn’t anticipating was the fact that her organization would have to fight to be involved in Covid vaccine distribution in the United States. The military was baked into the foundation of Operation Warp Speed, which not only spurred development of Covid vaccines but oversaw the rollout.

“I kind of thought that would be a done deal. I didn’t expect to have to advocate for that. I didn’t expect to have to fight for it,” Hannan said. “For me, that’s a ‘lessons learned.’ Existing systems, existing plans — in the heat of the moment, not everyone in a position of power knows about these plans and not everyone is ready to embrace something that they don’t understand or they haven’t been a part of developing.”

For Jeremy Farrar, incoming chief scientist at the WHO, the unequal access to Covid vaccines when they started to become available wasn’t a surprise, but the scale of the inequity was. “I did not expect countries would hoard vaccines they knew they were never going to use,” said Farrar, who is stepping down as director of the Wellcome Trust.

Pricey mRNA vaccines became the jab of choice in countries ill-equipped to use them

From the earliest days of the deployment of Covid vaccines, there were concerns about how challenging it was to use the mRNA vaccines, the first to generate proof that they worked. For starters, they needed ultra cold storage; Pfizer went so far as to make its own shipping cases that required dry ice to ensure precious doses weren’t lost to spoilage. And the vaccines were expensive; Pfizer currently charges the U.S. government $30.48 a dose while Moderna charges $26.36.

Those characteristics alone made the mRNA vaccines ill-suited for low-income countries where maintaining a regular cold chain — ensuring vaccines are stored at fridge temperature every step of the way — is a challenge. Ultra cold chain? Forget about it.

Researchers from the University of Oxford’s Jenner Institute specifically opted to design a vaccine that would be cheap to produce and easy to transport and store; AstraZeneca licensed and produced the Oxford vaccine. Peter Hotez and Maria Elena Bottazzi of Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine did the same; India’s Bharat Biotech made theirs. Both groups trumpeted their shots as the world’s vaccine, assuming there was enormous need for inexpensive and easy-to-use shots.

But it turned out that those in lower-income countries wanted what we were having. The health intelligence and analytics firm Airfinity estimated in October that 94% of the sales of Covid vaccines in 2023 will go to Pfizer-BioNTech and Moderna.

The world’s desire for mRNA vaccines surprised Seth Berkley, CEO of Gavi, the Vaccine Alliance. Gavi was a key player in COVAX, the organization set up by the WHO and other partners to buy and distribute vaccines to countries that couldn’t otherwise have procured them.

“We had good alternatives that were high efficacy and maybe even longer duration of protection and stable at regular room temperatures, etc. But countries want mRNA,” Berkley said.

He noted that AstraZeneca and Novavax vaccines produced by the Serum Institute of India cost $3 a dose. “The normal behavior would be that the low-priced, high-quality vaccines would replace the high-quality, much more expensive vaccines that are more difficult to use. But that didn’t happen.”