were protected after a single dose of the Pfizer vaccine and only 27 percent after a single dose of the AstraZeneca vaccine. (In Britain, the current practice is to delay second doses to stretch vaccine availability.)

Likewise, another study published last month indicated that fewer than 15 percent of patients with cancers of blood or the immune system, and fewer than 40 percent of those with solid tumors, produced antibodies after receiving a single dose of the Pfizer-BioNTech vaccine.

And a study published last month in the journal JAMA reported that only 17 percent of 436 transplant recipients who got one dose of the Pfizer-BioNTech or Moderna vaccine had detectable antibodies three weeks later.

Despite the low odds, immunocompromised people should still get the vaccines because they may produce some immune cells that are protective, even antibodies in a subset of patients.

“These patients should probably be prioritized for optimally timed two doses,” said Dr. Tariq Ahmad, a gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust who was involved in the infliximab studies.

He suggested that clinicians routinely measure antibody responses in immunocompromised people even after two vaccine doses, so as to identify those who also may need monoclonal antibodies to prevent infection or a third dose of the vaccines.

Wendy Halperin, 54, was diagnosed at age 28 with a condition called common variable immunodeficiency. She was hospitalized with Covid-19 in January and remained there for 15 days. But the coronavirus induced unusual symptoms.

“I was having trouble walking,” she recalled. “I just lost control of my limbs, like I couldn’t walk down the street.”

Because she was treated for Covid-19 with convalescent plasma, Ms. Halperin has had to wait three months to be immunized and has made an appointment for April 26. But despite her condition, her body did manage to produce some antibodies to the initial infection.

“The take home message is that everybody should try and get the vaccine,” said Dr. Amit Verma, an oncologist at Montefiore Medical Center.

The gamble did not pay off in Dr. Wollowitz’s case. Without antibodies in his system to protect him, he is still working from home — a privilege he is grateful for. He was an avid mountain biker and advanced skier, both of which carry risk of injury, but with the coronavirus, he is playing it safe.

In anticipation of returning to his normal lifestyle, Dr. Wollowitz is tuning his bicycles. But he said he foresaw himself living this way till enough other people are vaccinated and the number of infections in the city drops.

“I’m not exactly sure what that date is,” he said. “I’m really waiting to get back out.”

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Changing Strategy, the E.U. Bets Big on Pfizer to Battle Covid

BRUSSELS — Bruised by major disruptions in supplies of the AstraZeneca and Johnson & Johnson vaccines, the European Union Wednesday announced it was putting trust and money into the Pfizer-BioNTech shot to salvage its vaccination rollout and secure doses for the future.

The pivot away from AstraZeneca, once a pillar of the E.U. inoculation program, comes after months of discord over delayed shipments and as the company battles worries over rare potential side effects of its shots.

In announcing the change in strategy, Ursula von der Leyen, president of the European Commission, said Pfizer had agreed to an early shipment of doses that she said should likely allow the bloc to reach its goal of inoculating 70 percent of adults by the end of the summer.

That goal was in jeopardy after AstraZeneca failed to deliver on expected doses in the first quarter of the year, then suffered fresh setbacks over potential side effects related to blood clots. The European vaccine campaign was dealt a further blow Tuesday when Johnson & Johnson said it would delay its own rollout in Europe because of similar concerns and after regulators paused its use in the United States.

supply disruptions from AstraZeneca in late January, and then with the emergence of the potential rare blood disorder that has battered the public’s confidence in vaccines and led to appointment cancellations.

“As we can see with the announcement by Johnson & Johnson yesterday, there are still many factors that can disrupt the planned delivery schedules of vaccines,” Ms. von der Leyen said Wednesday.

Ms. von der Leyen said the Pfizer doses under negotiation for the next two years would include potential booster shots to extend the immunity of people who have already been inoculated, as well as possible new shots or boosters targeting emerging variants that might prove resilient against existing vaccines.

The AstraZeneca and Johnson & Johnson vaccines performed well in clinical trials and the possible dangerous side effects have been rare. But trials of the Pfizer and Moderna shots shows that they were even more effective in preventing infection, and similar side effects have not emerged. Another mRNA vaccine, from CureVac, is in clinical trials.

On Wednesday, the European Medicines Agency, the bloc’s top drug regulator, said it was expediting its investigation of “very rare cases of unusual blood clots” in recipients of the Johnson & Johnson vaccine, and expected to issue a recommendation next week. While the evaluation is ongoing, the agency reiterated its view that the benefits of the vaccine outweigh the risks.

In a setback for AstraZeneca, Denmark on Wednesday became the first country to permanently stop the administration of the company’s vaccine, saying the potential side effects were significant enough to do so given that it had the pandemic under control and could rely on the Pfizer and Moderna inoculations.

With the fresh commitment by Pfizer to bring forward the delivery of 50 million doses originally slated for the end of the year, the company expects to deliver 250 million doses in total to the bloc by the end of June.

Ms. von der Leyen said more than 100 million people in the European Union had already received at least one vaccine dose, and 27 million had received both. The additional Pfizer vaccines, together with 35 million doses expected from Moderna over the next three months, and a more limited use of AstraZeneca doses already in the pipeline, should likely be enough to get the bloc to the coveted milestone of reaching 255 million people by September, E.U. officials said.

In stark contrast to the criticism of AstraZeneca’s handling of its E.U. dealings, Ms. von der Leyen praised Pfizer effusively, highlighting how important the company’s ability to respond quickly to help the European Union has been.

“I want to thank BioNTech/Pfizer; it has proven to be a reliable partner,” Ms. von der Leyen said. “It has delivered on its commitments, and it is responsive to our needs.”

Addressing another sore point, Ms. von der Leyen said that the future Pfizer doses would be produced in the European Union.

Ample exports from the factories within the bloc to the rest of the world have enabled countries like Mexico and Canada to launch their vaccination campaigns, but those exports have also been identified as one reason there weren’t enough vaccines to go around in Europe.

The United States and Britain, by contrast, held tight to the vaccines made in their countries, helping speed along their inoculation efforts.

Monika Pronczukcontributed reporting.

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F.D.A. Will Allow Abortion Pills by Mail During the Pandemic

The Biden administration has decided to allow women to receive abortion pills by mail for the duration of the coronavirus pandemic, the latest development in an issue that has increasingly taken center stage in the American abortion debate.

In a letter sent Monday to two leading organizations representing reproductive health physicians, the acting commissioner of the Food and Drug Administration said that the agency would temporarily stop enforcing its requirement that the first of two drugs needed to terminate an early pregnancy be dispensed in a medical clinic.

The new policy counters a Supreme Court decision in January that sided with the Trump administration, which had appealed a federal judge’s decision last July to suspend the requirement. The judge had argued that the requirement put women at risk during the pandemic because they would need to visit clinics in person and often travel significant distances to do so.

Abortion through medication, first approved by the F.D.A. in 2000, is increasingly becoming women’s preferred method for terminating a pregnancy. As of 2017, research estimated that about 60 percent of abortion patients early enough in pregnancy to be eligible — 10 weeks pregnant or less — chose medication abortion over suction or surgery.

dispensed in clinics or hospitals by specially certified doctors or other medical providers. For years, reproductive health experts have urged that the requirement be lifted on the grounds that there are no significant safety reasons for in-person dispensing of a pill that women are then legally allowed to take on their own in any location, and that the restriction places the greatest burden on low-income women and those in areas with limited access to abortion providers.

For several years, with the F.D.A.’s permission, researchers have been conducting a study that provides telemedicine consultations to women seeking abortions and mails them the pills. Their research has found the approach to be safe and effective.

Additional data was collected in recent months from the experiences of women during the pandemic who received abortion pills by mail after the judge lifted the restriction and before the Supreme Court reinstated it.

Dr. Janet Woodcock, the acting F.D.A. commissioner, wrote in her letter to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine that studies of the pandemic experience “do not appear to show increases in serious safety concerns,” like bleeding, ectopic pregnancy or the need for surgical interventions “occurring with medical abortion as a result of modifying the in-person dispensing requirement during the Covid-19 pandemic.”

Groups that oppose abortion objected to the decision. Jeanne Mancini, president of March for Life, said in a statement that allowing appointments for medication abortion via telemedicine posed “grave danger” to women’s safety, adding “chemical abortions should have more medical oversight not less.”

letter in March to President Biden and Vice President Kamala Harris asking for the F.D.A. to lift the restrictions during the pandemic, welcomed the decision.

“Mifepristone itself has demonstrated, through both clinical study and decades of use, to be a safe, effective medication,” the president and chief executive of the American College of Obstetricians and Gynecologists said in a statement. “Requiring the medicine to be dispensed in person, then taken elsewhere at the patients’ discretion, is arbitrary and does nothing to bolster the safety of an already-safe medicine.”

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Worry Over 2 Covid Vaccines Deals Fresh Blow to Europe’s Inoculation Push

BRUSSELS — First it was AstraZeneca. Now Johnson & Johnson.

Last week, British regulators and the European Union’s medical agency said they had established a possible link between AstraZeneca’s Covid-19 vaccine and very rare, though sometimes fatal, blood clots.

On Tuesday, Johnson & Johnson said it would pause the rollout of its vaccine in Europe and the United States over similar concerns, further compounding the continent’s one-step-forward-two-steps-back efforts to quickly get people immunized against the coronavirus.

European officials had been confident that they had secured enough alternative vaccine doses to take up the slack of the AstraZeneca problems and achieve their goal of fully inoculating 70 percent of the European Union’s adult population — about 255 million people — by the end of the summer.

On Tuesday, European officials did not immediately say whether they believed the milestone would also survive the Johnson & Johnson suspension. But the European commissioner for health, Stella Kyriakides, wrote on Twitter that “Today’s developments with the J&J vaccine in the US are under close monitoring” by the bloc’s medicines regulator.

months of short supplies and logistical problems.

There is mounting evidence that the concerns are eroding Europeans’ willingness to get the AstraZeneca vaccine in particular, and threatening to elevate already high levels of vaccine hesitancy generally.

YouGov poll published last month, 61 percent of the French, 55 percent of Germans and 52 percent of Spaniards consider the AstraZeneca vaccine “unsafe.” That is in stark contrast to the findings of a similar poll from February, when more people in those countries, with the exception of France, believed that the shot was more safe than unsafe.

Regulators have asked vaccine recipients and doctors to be on the lookout for certain symptoms, including severe and persistent headaches and tiny blood spots under the skin. Doctors’ groups have circulated guidance about how to treat the disorder.

In Poland, where the vaccination campaign relies to a large extent on AstraZeneca and where its use has not been restricted, a recent poll showed that given a choice, fewer than 5 percent of Poles would choose the AstraZeneca shot.

Almost everywhere across the European Union, it seems, many are eager for alternatives, as the new types of vaccines that include the Moderna and Pfizer, which utilize science known as “mRNA,” have not been associated with similar side effects.

Data from the 27 E.U. member states by the European Center for Disease Prevention and Control shows that over all, 80 percent of vaccine doses distributed to the bloc have already been administered. That share drops to 65 percent for AstraZeneca, however, suggesting that many of its doses are sitting unused.

Yet it is hard to predict how serious a blow the latest twist in the AstraZeneca saga — and the new Johnson & Johnson concerns — will be to E.U. vaccination efforts, as officials in Brussels have made big if belated efforts to turbocharge the second-quarter supply of doses.

The European Union is poised to receive at least 300 million doses of various vaccines, three times what it got in the first quarter. Two hundred million are slated to come from Pfizer/BioNTech. Moderna is expected to deliver 35 million doses. Another 55 million doses are due of the Johnson & Johnson jab, and 70 million from AstraZeneca.

In the rosiest scenario, the European Union could get up to 360 million doses by June.

On Thursday, after Spain’s government changed the age threshold for the AstraZeneca shot, two-thirds of people called up for vaccination in Madrid did not show up, Antonio Zapatero, the regional health minister, told a news conference on Friday.

He attributed the no-show by 18,200 people to “confusion” generated by Spain’s central government, which said on Wednesday that the AstraZeneca vaccine should be given only to people over 60. Before this change, Mr. Zapatero said, the rate of abstention was 2 percent.

In Belgium, where the use of the AstraZeneca vaccine has also been limited, the authorities said they did not expect major delays in the overall rollout, but they are still concerned about the confusion that the rare blood clotting issue is causing.

Yves Van Laethem, a top epidemiologist who is the country’s Covid task force spokesman, said he expected a two-week delay that would mostly affect younger age groups in late summer. He said the E.U. regulator guidance had only partly helped in clarifying the situation.

The European Medicines Agency’s opinion “wasn’t very clear, and it is also part of the problem,” Dr. Van Laethem said in an interview. “When you say, ‘We don’t apply limitations, but we just say there are serious side effects,’ there is part science and part diplomacy in that.”

He said the limited effect that the new AstraZeneca issues would have on Belgian’s rollout was in large part because the country had ordered big shares of other vaccines.

Although all E.U. countries have been offered a chunk of each vaccine approved in the bloc so far — AstraZeneca, Johnson & Johnson, Moderna and Pfizer — many opted to forgo parts of their share of more expensive or cumbersome vaccines like Pfizer and Moderna early on, instead favoring the AstraZeneca jab.

“In Britain or Eastern Europe, a big part of the campaigns are based on AstraZeneca,” Dr. Van Laethem said.

Wealthier bloc members like Denmark, France, Germany and the Netherlands can better compensate for the loss of confidence in AstraZeneca, because they acquired extra doses of other vaccines — especially Pfizer — through a secondary market after poorer E.U. nations gave theirs up.

Those countries — including Bulgaria, Croatia, Latvia and Slovakia — are likely to be less able to quickly offer alternatives.

Dr. Van Laethem, the Belgian immunologist, said that the national and European authorities needed to better communicate the costs and benefits of taking the AstraZeneca dose versus and the other authorized vaccines.

Experts worry that even limited concerns over one vaccine’s unlikely side effects can affect people’s overall willingness to be immunized.

“The main thing is to make people understand that the problem is the virus,” he said. “We have to vaccinate people — the risk linked to the virus is higher than those rare side effects.”

Raphael Minder contributed reporting from Madrid and Constant Méheut from Paris.

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China Official Acknowledges Low Effectiveness of the Country’s Covid Vaccines

A senior Chinese official said that the country’s vaccines may need to be administered in greater doses or in concert with other shots because of their low overall effectiveness.

The comments on Saturday by Gao Fu, the director of China’s disease control center, suggest that China and more than 60 countries that have approved Chinese vaccines could need to adjust their distribution programs. The widespread distribution of Chinese vaccines means that any changes could potentially affect hundreds of millions of people or more.

Possible steps to boost effectiveness of Chinese vaccines include changing the amount of vaccine given, the number of shots, the time between shots or the type of vaccines given, Mr. Gao said.

He also praised the possibilities offered by messenger RNA. That technology is used in the Moderna and Pfizer-BioNTech vaccines but not in any of the vaccines thus far approved in China.

said in January that the efficacy rate for the CoronaVac vaccine from the Beijing-based company Sinovac was just over 50 percent. By comparison, Moderna and Pfizer-BioNTech were found to be 90 percent effective in real world conditions, researchers said last month.

Last month the distributor in the United Arab Emirates of vaccines from China’s Sinopharm said it was offering a third dose in addition to the standard two-dose regimen for a “very small number” of people who were “not really responsive” to the vaccine.

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Slovakia Claims a Bait-and-Switch With the Russian Vaccines it Ordered

The European Union’s regulator, the European Medicines Agency, has so far declined to approve the Russian vaccine for use and only two members of the bloc, Hungary and Slovakia, have placed orders for Sputnik V. Serbia, which is not a member of the bloc, has also ordered Sputnik V and begun using it in a mass inoculation program that has been far more successful than the stumbling efforts of most European Union states.

Even Germany, a stickler for procedure, has expressed growing interest in Sputnik V. Health Minister Jens Spahn told the public broadcaster WDR on Thursday that he would like to start bilateral talks with Russia over a potential purchase of the vaccine, which would go through only if it is approved by the European Medicines Agency.

The previous day, Markus Söder, the governor of Bavaria, said his government had signed a preliminary agreement to buy 2.5 million doses of the vaccine, which are to be produced at a Russian-owned plant in the southern state. That deal, too, is contingent on E.M.A. approval.

Sputnik V is manufactured at seven locations in Russia, and also at plants in India and South Korea. A number of other countries have signed manufacturing contracts, including Brazil, Turkey and Serbia. Russia has consistently delivered fewer doses of the vaccine than initially promised, suggesting glitches in manufacturing. Producing vaccines at scale is a difficult process and ramping up production has presented problems for Western vaccines, too.

Noting that about 40 countries are using or scheduled to use the Russian vaccine, the Slovak regulatory agency asserted that “these vaccines are only associated by the name.” That raised questions about deviations from the formula reviewed in The Lancet.

“The comparability and consistency of different batches produced at different locations has not been demonstrated,” the Slovak regulator said. “In several cases, they appear to be vaccines with different properties (lyophilisate versus solution, single-dose ampoules versus multi-dose vials, different storage conditions, composition and method of manufacture).”

The Slovak statement could damage Russia’s efforts to establish Sputnik V as a reliable brand. It could also exacerbate lingering doubts left by the vaccine’s highly politicized rollout in Russia, where President Vladimir V. Putin announced that the drug was ready for use in August, before clinical trials had finished.

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Researchers Are Hatching a Low-Cost Covid-19 Vaccine

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

Vaccines work by acquainting the immune system with a virus well enough to prompt a defense against it. Some vaccines contain entire viruses that have been killed; others contain just a single protein from the virus. Still others contain genetic instructions that our cells can use to make the viral protein.

Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.

spike, latches onto cells and then allows the virus to fuse to them.

But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. That’s because spike proteins sometimes assume the wrong shape, and prompt the immune system to make the wrong antibodies.

The researchers injected the 2P spikes into mice and found that the animals could easily fight off infections of the MERS coronavirus.

The team filed a patent for its modified spike, but the world took little notice of the invention. MERS, although deadly, is not very contagious and proved to be a relatively minor threat; fewer than 1,000 people have died of MERS since it first emerged in humans.

But in late 2019 a new coronavirus, SARS-CoV-2, emerged and began ravaging the world. Dr. McLellan and his colleagues swung into action, designing a 2P spike unique to SARS-CoV-2. In a matter of days, Moderna used that information to design a vaccine for Covid-19; it contained a genetic molecule called RNA with the instructions for making the 2P spike.

Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and starting clinical trials. All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

But once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innes and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own.

experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

Meanwhile, the Mount Sinai team has also licensed the vaccine to the Mexican vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

To the nations involved, the prospect of making the vaccines entirely on their own was appealing. “This vaccine production is produced by Thai people for Thai people,” Thailand’s health minister, Anutin Charnvirakul, said at the announcement in Bangkok.

In Brazil, the Butantan Institute trumpeted its version of NDV-HXP-S as “the Brazilian vaccine,” one that would be “produced entirely in Brazil, without depending on imports.”

Ms. Taylor, of the Duke Global Health Innovation Center, was sympathetic. “I could understand why that would really be such an attractive prospect,” she said. “They’ve been at the mercy of global supply chains.”

Madhavi Sunder, an expert on intellectual property at Georgetown Law School, cautioned that NDV-HXP-S would not immediately help countries like Brazil as they grappled with the current wave of Covid-19 infections. “We’re not talking 16 billion doses in 2020,” she said.

Instead, the strategy will be important for long-term vaccine production — not just for Covid-19 but for other pandemics that may come in the future. “It sounds super promising,” she said.

In the meantime, Dr. McLellan has returned to the molecular drawing board to try to make a third version of their spike that is even better than HexaPro.

“There’s really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you’d have to say, ‘This is the next generation.’”

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Researchers Are Hatching a Low-Cost Coronavirus Vaccine

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

Vaccines work by acquainting the immune system with a virus well enough to prompt a defense against it. Some vaccines contain entire viruses that have been killed; others contain just a single protein from the virus. Still others contain genetic instructions that our cells can use to make the viral protein.

Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.

spike, latches onto cells and then allows the virus to fuse to them.

But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. That’s because spike proteins sometimes assume the wrong shape, and prompt the immune system to make the wrong antibodies.

The researchers injected the 2P spikes into mice and found that the animals could easily fight off infections of the MERS coronavirus.

The team filed a patent for its modified spike, but the world took little notice of the invention. MERS, although deadly, is not very contagious and proved to be a relatively minor threat; fewer than 1,000 people have died of MERS since it first emerged in humans.

But in late 2019 a new coronavirus, SARS-CoV-2, emerged and began ravaging the world. Dr. McLellan and his colleagues swung into action, designing a 2P spike unique to SARS-CoV-2. In a matter of days, Moderna used that information to design a vaccine for Covid-19; it contained a genetic molecule called RNA with the instructions for making the 2P spike.

Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and starting clinical trials. All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

But once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innes and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own.

experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

Meanwhile, the Mount Sinai team has also licensed the vaccine to the Mexican vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

To the nations involved, the prospect of making the vaccines entirely on their own was appealing. “This vaccine production is produced by Thai people for Thai people,” Thailand’s health minister, Anutin Charnvirakul, said at the announcement in Bangkok.

In Brazil, the Butantan Institute trumpeted its version of NDV-HXP-S as “the Brazilian vaccine,” one that would be “produced entirely in Brazil, without depending on imports.”

Ms. Taylor, of the Duke Global Health Innovation Center, was sympathetic. “I could understand why that would really be such an attractive prospect,” she said. “They’ve been at the mercy of global supply chains.”

Madhavi Sunder, an expert on intellectual property at Georgetown Law School, cautioned that NDV-HXP-S would not immediately help countries like Brazil as they grappled with the current wave of Covid-19 infections. “We’re not talking 16 billion doses in 2020,” she said.

Instead, the strategy will be important for long-term vaccine production — not just for Covid-19 but for other pandemics that may come in the future. “It sounds super promising,” she said.

In the meantime, Dr. McLellan has returned to the molecular drawing board to try to make a third version of their spike that is even better than HexaPro.

“There’s really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you’d have to say, ‘This is the next generation.’”

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A ‘Game Changer’ for Patients With Esophageal Cancer

The chemotherapy has difficult side effects, and the radiation causes a burning sensation that makes it difficult to swallow. “Food won’t go down,” Ms. Mordecai said. “You just feel rotten.”

The next step is major surgery. A doctor takes out most of the patient’s esophagus, the tract leading from the mouth to the stomach, and then grabs the stomach and pulls it up, attaching it to a stump of esophagus left behind.

The result is a stomach that is vertical, not horizontal, and lacks the sphincter muscle that normally keeps stomach acid from spilling out. For the rest of their lives, patients can never lie flat — if they do, the contents of their stomach, including acid, pours into their throats. They can choke, cough and aspirate.

Recovery is difficult, and morbidity and mortality are high. But most patients go through with the operation once they weigh their options. To refuse the treatment means giving up and letting the cancer close off the esophagus to the point where some cannot even swallow their own saliva, said Dr. Paul Helft, a professor of surgery and an ethicist at Indiana University School of Medicine.

The treatment is so long and harrowing that Dr. Helft often uses it to teach medical students and other trainees about informed consent — about how patients must be fully informed before they start any given treatment. Esophageal cancer patients in particular must be told that they are likely to have a recurrence within the first year.

Ms. Mordecai said her husband had his surgery at the end of September 2008. By Dec. 6, he had untreatable metastases in his liver. Now, she said, patients may have a glimmer of hope.

Dr. Ilson, who has spent his career trying to develop therapies to help patients with esophageal cancer, said that he did not expect this treatment to succeed: “We all get nihilistic when faced with years of negative studies.”

“This is really a landmark paper,” he added, and the drug “will become a new standard of care.”

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José Baselga, Who Advanced Breast Cancer Treatments, Dies at 61

José Baselga was born in Barcelona on July 3, 1959, and earned his medical and doctoral degrees from the Autonomous University of Barcelona. He caught the attention of cancer researchers after participating in a medical fellowship at Memorial Sloan Kettering, where he worked with Dr. John Mendelsohn in researching the use of monoclonal antibodies in targeting certain proteins associated with aggressive cancers, including lung and breast cancers.

Dr. Larry Norton, a senior vice president at Memorial Sloan Kettering and the medical director of the hospital’s Evelyn H. Lauder Breast Center, quickly took an interest in Dr. Baselga and served as an early mentor. “He was an artist,” Dr. Norton recalled, adding that he had “a driving force within him, and he would focus all of his energies on accomplishing what was necessary to fulfill that vision.”

Dr. Baselga returned to Spain in 1996 to found the Vall d’Hebron Institute of Oncology at Vall d’Hebron University Hospital in Barcelona. Under his leadership, the center became an international powerhouse in cancer research, testing targeted cancer therapies in early-stage clinical trials. Dr. Baselga became a well-known figure in Spain.

“Spain was not known in the world as a cancer research place,” Dr. Antoni Ribas, the president of the American Association for Cancer Research, who did his medical residency at Vall d’Hebron just before Dr. Baselga assumed his role there, said in a phone interview. “He put Vall d’Hebron, Barcelona and Spain on the map of cancer research.”

Following a stint from 2010 to 2013 at Massachusetts General Hospital, where he was the chief of the division of hematology and oncology, Dr. Baselga returned to Memorial Sloan Kettering in 2013 to become physician in chief and, later, chief medical officer.

He also held several leadership roles in the world of cancer research, including president of the American Association for Cancer Research and editor of Cancer Discovery and other medical journals.

Dr. Baselga resigned from Sloan Kettering in September 2018 under pressure after The Times and ProPublica, the nonprofit investigative journalism outfit, reported that he had failed to disclose millions of dollars in payments from drug and health care companies in dozens of research articles in The New England Journal of Medicine and other publications.

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