Operation Warp Speed, the Trump-era program that poured billions of dollars into developing Covid vaccines, seemed to signal a new dawn in American vaccine manufacturing, demonstrating how decades of hard scientific work could translate into life-saving drugs in matter of months.
As a third pandemic winter begins in the United States, however, its vaccine production effort has run out of steam.
Efforts to test and produce next-generation Covid vaccines are bogged down by bureaucratic problems and lack of funding.
Foreign rivals have rushed to approve long-awaited nasal spray vaccines, including one invented in St. Louis, creating a scenario where Americans would have to travel abroad to obtain the latest in American vaccine technology.
The Joe Biden administration has launched a last-ditch effort to restore the country’s lead. In an attempt to resurrect Operation Warp Speed [algo como “velocidade espacial”]the president asked the interim session of Congress this week for $5 billion for next-generation vaccines and therapeutics, as part of a broader pandemic spending request of $9.25 billion.
But Republicans, having blocked funding requests for next-generation vaccines since the spring amid complaints about how the White House has spent past pandemic aid allocations, have shown no signs of easing their resistance.
As a result, even as the pandemic still takes a heavy toll, the prospects for the two most coveted types of next-generation vaccines have dimmed: nasal sprays capable of blocking more infections and universal coronavirus vaccines, which can protect against a wider range of evolving variants.
In the coming months, scientists predict that Covid could kill tens of thousands of Americans. The cost of infections also continues to rise: Covid patients have long struggled with persistent health problems. And millions are losing their jobs because they caught the virus, compounding the labor shortage.
No next-generation vaccine is as available or as likely to reduce the spread of the virus as those that can be inhaled or sprayed into the nose.
By generating immunity in people’s airways, where the coronavirus arrives first, these vaccines could potentially help extinguish infections before they start. The immunity provided by an injection in the arm, on the other hand, takes longer to attack the invading virus, giving people good protection against serious illness but not against the infections that spread the virus and let it evolve.
China, India, Russia and Iran have approved vaccines given through the nose or mouth, although they haven’t released much data on how the products work.
In the United States, nasal sprays have been held back by the same funding constraints and logistical problems that, before the pandemic, often made vaccine development a decade-long quest. The delay could not only weaken the country’s defenses against a more deadly variant of the coronavirus, but also hamper preparations for a future pandemic, depriving the world of a ready-made nasal vaccine platform that could be adapted to a new pathogen.
“It’s back to the pre-pandemic speed of vaccine development,” said Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai Hospital. His team nasal vaccine has passed its most advanced trials in Mexico; collaborating with a pharmaceutical company there offered the fastest path to funding clinical trials. In the United States, he said, “the funding situation is dire.”
The problems are not just financial. The best next-generation vaccine studies often rely on using existing mRNA injections, such as the Covid vaccines made by Pfizer and Moderna. In some cases, this is because researchers want to compare nasal sprays with injectable vaccines. In others, it’s because scientists need to know how much the nasal vaccines boost immunity after a previous mRNA injection.
But scientists aiming to develop nasal vaccines as boosters have found they are barred from using leftover doses from Pfizer or Moderna in their studies, despite tens of millions of unused doses being thrown away.
Agreements with the federal government prevent doses of the two vaccines from being used for research purposes without the companies’ approval, scientists said. These types of provisions are generally intended to protect companies from the risk of a poorly executed experiment damaging their product, although they can also help protect companies from studies that could benefit a competitor.
Because the government controls the supply of injections from Pfizer and Moderna, nasal vaccine makers cannot purchase them independently. Instead, the scientists had to pay outside manufacturers to make imitations.
Among the researchers in this position is Akiko Iwasaki, an immunologist at Yale University, whose experimental nasal vaccine aims to boost immunity in those previously injected with mRNA vaccines. Her team’s vaccine appears to reduce viral transmission in hamsters, a promising sign. But Dr. Iwasaki couldn’t get injections from Pfizer or Moderna for studies in monkeys, creating less reliable conditions for measuring how animals receiving mRNA injections respond to nasal boosts.
“There are millions of doses going down the drain, and all we ask for is a few vials so we can do research on animals,” Dr. Iwasaki said. “It pretty much stopped us.”
Federal government scientists have struggled to overcome the same legal barriers, despite broad taxpayer support for mRNA vaccines. For much of the past year, federal officials have been negotiating with Moderna for permission to use its vaccine in research studies that were not expressly approved by Moderna or done in collaboration with the company, said Karin Bok, acting deputy director of the Center for Research in Vaccines from the National Institute of Allergy and Infectious Diseases.
Only about a month ago did government scientists receive these doses, said Dr. Bok. They still can’t use Pfizer’s vaccine in the same way, she added.
“That’s a big gap we need to think about to get through the next pandemic,” Bok said. For now, she said, nasal vaccine makers and other researchers are unlikely to get licensed mRNA vaccines until doses are available privately next year.
Pfizer said in a statement that it was not supplying its vaccine to independent research groups, but that it had worked with governments that wanted to resell or donate doses for clinical trials. Moderna said it evaluated research requests on a case-by-case basis and collaborated with government scientists and several academic labs on studies of its vaccines.
There are no guarantees about the effectiveness of a nasal vaccine or how long its protections would last. It’s not entirely clear how best to formulate the vaccines or deliver them to people’s airways. Safety concerns stem from the proximity of the nasal cavity to the brain and lungs. And there is no standard test for measuring immune responses in the airways, as there is for measuring systemic immunity that is the goal of injectable vaccines.
The only nasal vaccine approved in the United States is FluMist, to prevent the flu, and its use is restricted to young, healthy people.
Last month, a nasal version of the Oxford-Astrazeneca vaccine failed a test, which investigators said could have resulted from too much spray being swallowed and broken down in the stomach.
“It’s a fundamentally more difficult undertaking than an injection in the arm, which we’ve been doing for over a hundred years,” said Dr. Benjamin Goldman-Israelow of Yale, who is working with Dr. Iwasaki on the team’s nasal vaccine.
The chances of any candidate failing have discouraged the biggest US vaccine makers from investing. While government funding protected pharmaceutical companies in 2020 from the risks of pouring money into complicated vaccine research, those guarantees have evaporated.
The Covid vaccine market has also become less welcoming to newcomers, industry experts say: Pfizer and Moderna vaccines dominate, giving those companies little reason to spend big on a competing vaccine and deter their rivals.
Foreign manufacturers have shown more interest, in part because nasal vaccines are expected to be easier to store and use than mRNA injections in poorer countries. Eventually, people may even be able to self-administer them at home.
Two years ago, leading Indian laboratory Bharat Biotech launched a promising early study of a nasal vaccine designed at Washington University in St. Louis and negotiated the manufacturing and testing of doses. India recently approved the vaccine based on data that Bharat has submitted to US government scientists but has not released publicly.
The vaccine has progressed more slowly in the United States. Only last month did a smaller US company, Ocugen, secure the rights to it.
The team behind the vaccine “made several invitations to almost all of the key vaccine participants and there was no uptake,” said Dr. David T. Curiel, a researcher at Washington University in St. Louis. Louis, who invented the vaccine with a colleague, Dr. Michael Diamond. Curiel said the White House had long asked for funding to develop vaccines. But, he said, “the Orwellian aspect has been trying to find out specifically where those funds are.”
Government scientists have been pushing to speed up the process. Dr. Robert Seder of the Vaccine Research Center has recently begun a study in non-human primates that will compare different nasal booster formulations with each other and with injectable boosters. He will also test spraying the new vaccines into the nose or inhaling through a mouthpiece.
One candidate is a modified version of Moderna’s shot. The company said it was collaborating with government scientists and studying how to deliver mRNA drugs to the lungs.
But federal health officials said they too have seen funding requests dwindle, leaving much of the burden on academic researchers and their start-ups. About half a dozen American groups are testing nasal vaccines in people.
“We don’t have the resources of a Pfizer or BioNTech,” said Dr. Bruce Turner, CEO of Xanadu Bio, which he founded with Dr. Iwasaki at Yale. “We don’t have Operation Warp Speed.”
America’s leading nasal vaccine candidates were built on decades of government funding for research. What is needed, scientists say, is money to get these vaccines out of university labs and into real-world studies now that they are sorely needed.
“We are in the last mile,” said Biao He, a professor at the University of Georgia. His company, Athens, Georgia-based CyanVac, began an early-stage human study of a nasal vaccine 15 months ago, which is only now nearing completion. The costs of speeding up testing, he said, pale in comparison to the risks of waiting.
“When so many people’s lives are at stake, can’t we do something about it?” he said.
Translated by Luiz Roberto M. Gonçalves
I have over 8 years of experience in the news industry. I have worked for various news websites and have also written for a few news agencies. I mostly cover healthcare news, but I am also interested in other topics such as politics, business, and entertainment. In my free time, I enjoy writing fiction and spending time with my family and friends.
