“The attitude here is more, ‘Get me out of the pandemic,’” said Penny Ward, a visiting professor in pharmaceutical medicine at King’s College London, referring to the British approach. In continental Europe, she said, “There seems to be a much higher emphasis on individual safety in the population.”

Adriano Mannino, a philosopher at the University of Munich and director of the Solon Center for Policy Innovation in Germany, said that the collective benefits of the vaccine dominated thinking in Britain, while Germans were more concerned with the risk of an injection going wrong in individual cases. That reflected, partly, Germany’s history with the Nazis, who conducted lethal experiments on people.

“In many areas where law has to regulate ethically delicate and potentially dangerous things,” he said, “the German state has tended to go for tough restrictions.”

Nevertheless, Germans over 60 — the age group still being given AstraZeneca’s vaccine — flooded hotlines to book appointments and stood in line for hours in recent days as eligibility restrictions for their age group were relaxed.

In the northeastern city of Wismar, several hundred people waited for up to five hours on Tuesday in a driving wind and mix of rain and snow to receive the shot.

“I wish there had been better weather,” Kerstin Weiss, the head of the district authority in the northeastern region, told public broadcaster NDR. “But honestly, this is a sign that people are willing to be vaccinated with AstraZeneca.”

Benjamin Mueller reported from London and Melissa Eddy from Berlin. Monika Pronczuk and Emma Bubola contributed reporting.

View Source

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.’”

View Source

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.’”

View Source

Virus Variants Threaten to Draw Out the Pandemic, Scientists Say

For weeks, the mood in much of the United States has been buoyant. Cases, hospitalizations and deaths from the coronavirus have fallen steeply from their highs, and millions of people are being newly vaccinated every day. Restaurants, shops and schools have reopened. Some states, like Texas and Florida, have abandoned precautions altogether.

In measurable ways, Americans are winning the war against the coronavirus. Powerful vaccines and an accelerating rollout all but guarantee an eventual return to normalcy — to backyard barbecues, summer camps and sleepovers.

But it is increasingly clear that the next few months will be painful. So-called variants are spreading, carrying mutations that make the coronavirus both more contagious and in some cases more deadly.

Even as vaccines were authorized late last year, illuminating a path to the pandemic’s end, variants were trouncing Britain, South Africa and Brazil. New variants have continued to pop up — in California one week, in New York and Oregon the next. As they take root, these new versions of the coronavirus threaten to postpone an end to the pandemic.

rising exponentially in the United States.

Limited genetic testing has turned up more than 12,500 cases, many in Florida and Michigan. As of March 13, the variant accounted for about 27 percent of new cases nationwide, up from just 1 percent in early February.

pledged a “down payment” of $200 million to ramp up surveillance, an infusion intended to make it possible to analyze 25,000 patient samples each week for virus variants. It’s an ambitious goal: The country was sequencing just a few hundred samples each week in December, then scaling up to about 9,000 per week as of March 27.

Until recently, B.1.1.7’s rise was camouflaged by falling rates of infection over all, lulling Americans into a false sense of security and leading to prematurely relaxed restrictions, researchers say.

“The best way to think about B.1.1.7 and other variants is to treat them as separate epidemics,” said Sebastian Funk, a professor of infectious disease dynamics at the London School of Hygiene and Tropical Medicine. “We’re really kind of obscuring the view by adding them all up to give an overall number of cases.”

Other variants identified in South Africa and Brazil, as well as some virus versions first seen in the United States, have been slower to spread. But they, too, are worrisome, because they contain a mutation that diminishes the vaccines’ effectiveness. Just this week, an outbreak of P.1, the variant that crushed Brazil, forced a shutdown of the Whistler Blackcomb ski resort in British Columbia.

as fast as possible.

Infections are rising again, driven to an uncertain degree by B.1.1.7 and other variants. Earlier this week, Dr. Rochelle Walensky, director of the Centers for Disease Control and Prevention, pleaded with Americans to continue to practice masking and social distancing, saying she felt a sense of “impending doom.”

60 percent more contagious and 67 percent more deadly than the original form of the virus, according to the most recent estimates.

The variant is no different from the original in how it spreads, but infected people seem to carry more of the virus and for longer, said Katrina Lythgoe, an evolutionary biologist at the University of Oxford. “You’re more infectious for more days,” she said.

So contagious is B.1.1.7 that Britain succeeded in driving down infections only after nearly three months of strict stay-at-home orders, plus an aggressive vaccination program. Even so, cases fell much more slowly than they did during a similar lockdown in March and April.

three-quarters of new infections, some hospitals have had to move coronavirus patients to Belgium to free up beds. Roughly as many people are dying each day from Covid-19 in Europe as were this time a year ago.

For too long, government officials disregarded the threat. “Case plateaus can hide the emergence of new variants,” said Carl Pearson, a research fellow at the London School of Hygiene and Tropical Medicine. “And the higher those plateaus are, the worse the problem is.”

In the United States, coronavirus infections began a rapid decline in January, soon prompting many state leaders to reopen businesses and ease restrictions. But scientists repeatedly warned that the drop would not last. After the rate bottomed out at about 55,000 cases and 1,500 deaths per day in mid-March, some states — notably Michigan — began seeing an uptick.

Since then, the national numbers have steadily risen. As of Saturday, the daily count was up to nearly 69,000, and the weekly average was 19 percent higher than the figure two weeks earlier.

Pfizer-BioNTech and Moderna vaccines seem to be slightly less effective against B.1.351, the variant identified in South Africa. That variant contains the Eek mutation, which seems to enable the virus to partly sidestep the body’s immune response. The vaccines made by Johnson & Johnson, AstraZeneca and Novavax were even less potent against B.1.351.

“I think for the next year or two, E484K will be the most concerning” mutation, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.

The mutation slightly alters the so-called spike protein sitting on the surface of the coronavirus, making it just a bit harder for antibodies to latch on and destroy the invader.

The good news is that the virus seems to have just a few survival tricks in its bag, and that makes it easier for scientists to find and block those defenses. “I’m feeling pretty good about the fact that there aren’t that many choices,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York.

The Eek mutation seems to be the virus’s primary defense against the immune system. Researchers in South Africa recently reported that a new vaccine directed against B.1.351 ought to fend off all other variants, as well.

Pfizer, BioNTech and Moderna already are testing newly designed booster shots against B.1.351 that should work against any variants known to blunt the immune response.

Instead of a new vaccine against variants, however, it may be just as effective for Americans to receive a third dose of the Pfizer-BioNtech or Moderna vaccines in six months to a year, said Dr. Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases.

That would keep antibody levels high in each recipient, overwhelming any variant — a more practical strategy than making a specialized vaccine for each new variant that emerges, he said.

“My only concern about chasing all the variants is that you’d almost be playing Whac-A-Mole, you know, because they’ll keep coming up and keep coming up,” Dr. Fauci said.

In one form or another, the new coronavirus is here to stay, many scientists believe. Multiple variants may be circulating in the country at the same time, as is the case for common cold coronaviruses and influenza. Keeping them at bay may require an annual shot, like the flu vaccine.

The best way to deter the emergence of dangerous variants is to keep cases down now and to immunize the vast majority of the world — not just the United States — as quickly as possible. If significant pockets of the globe remain unprotected, the virus will continue to evolve in dangerous new ways.

“This might be something that we have to deal with for a long time,” said Rosalind Eggo, an epidemiologist at London School of Hygiene and Tropical Medicine.

Still, she added, “Even if it changes again, which it is very likely to do, we are in a better, much stronger position than a year ago to deal with it.”

View Source

The Pfizer-BioNTech Vaccine Is Said to Be Powerfully Protective in Adolescents

The Pfizer-BioNTech coronavirus vaccine is extremely effective in adolescents 12 to 15 years old, perhaps even more so than in adults, the companies reported on Wednesday. No infections were found among children who received the vaccine in a recent clinical trial, the drug makers said; the children produced strong antibody responses and experienced no serious side effects.

The findings, if they hold up, may speed a return to normalcy for millions of American families. Depending on regulatory approval, vaccinations could begin before the start of the next academic year for middle school and high school students, and for elementary school children not long after.

The companies announced the results in a news release that did not include detailed data from the trial, which has not yet been peer-reviewed nor published in a scientific journal. Still, the news drew praise and excitement from experts.

“Oh my god, I’m so happy to see this — this is amazing,” said Akiko Iwasaki, an immunologist at Yale University. If the vaccines’s performance in adults was A-plus, the results in children were “A-plus-plus.”

had left her with sense of “impending doom,” while President Biden called on state and local officials to reinstate mask mandates.

Vaccination efforts are accelerating throughout the nation. As of Tuesday, 29 percent of adults had received at least one dose of a coronavirus vaccine, and 16 percent had been fully inoculated, according to the C.D.C.

But the country cannot hope to reach herd immunity — the point at which immunity becomes so widespread that the coronavirus slows its crawl through the population — without also inoculating the youngest Americans, some experts say. Children under 18 account for about 23 percent of the population in the United States.

“The sooner that we can get vaccines into as many people as possible, regardless of their age, the sooner we will be able to really feel like we’re ending this pandemic for good,” said Angela Rasmussen, a virologist affiliated with Georgetown University in Washington.

Data from Israel suggest that vaccinating adults alone can significantly decrease the number of cases, but “long term, to hit the herd immunity threshold, we will have to vaccinate children,” she said.

children ages 5 to 11 just last week. Company scientists plan to start testing the vaccine next week in even younger children, ages 2 to 5, followed by trials in children ages 6 months to 2 years.

testing its vaccine in children. Results from a trial in adolescents ages 12 to 17 are expected in the next few weeks and in children 6 months to 12 years old in the second half of this year.

AstraZeneca started testing its vaccine in children 6 months and older last month, and Johnson & Johnson has said it will wait for results from trials in older children before testing its vaccine in children under 12.

Some parents have said they are reluctant to immunize their children because the risk posed by the virus is low. Children make up fewer than 1 percent of deaths from Covid-19, but about 2 percent of children who get the illness require hospital care.

The new results may not sway all of those parents, but they may reassure parents who have been wary of the vaccines, said Jennifer Nuzzo, an epidemiologist at the Johns Hopkins Center for Health Security.

“While I don’t think we have to wait until children are vaccinated to fully reopen schools, being able to vaccinate children may help some families feel safer about returning to school,” she said.

Pfizer and BioNTech plan to request from the Food and Drug Administration an amendment to the emergency use authorization for their vaccine, in hopes of beginning immunizations of older children before the start of the next school year. The companies also are planning to submit their data for peer review and publication in a scientific journal.

They will monitor the participants for two years after the second dose to assess the vaccine’s long-term safety and efficacy. Side effects of vaccines are usually apparent within the first six weeks, said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York. “Still, it’s good to know that safety monitoring is going to continue,” she said.

The C.D.C. recommends that people avoid getting other vaccines for two weeks before and after receiving the two doses of the coronavirus vaccine.

But children receive more vaccines in the few weeks before the school year than at any other time, Dr. Oliver noted, so pediatricians and parents should aim to get those other immunizations done earlier than usual.

The coronavirus vaccines should ideally be given by pediatricians who have deep experience in immunizing children, Dr. Oliver added. “Now is the time to start planning how that rollout is going to take place in this age group,” she said.

View Source