Tagged Antibodies

Studies Suggest People Who Had Covid-19 Should Get Single Vaccine Dose

People Who Have Had Covid Should Get Single Vaccine Dose, Studies Suggest

New studies show that one shot of a vaccine can greatly amplify antibody levels in those who have recovered from the coronavirus.

A nurse supervisor prepared a dose of the Pfizer-BioNTech vaccine at a mass vaccination site in Hartford, Conn., this month.
A nurse supervisor prepared a dose of the Pfizer-BioNTech vaccine at a mass vaccination site in Hartford, Conn., this month.Credit…Christopher Capozziello for The New York Times
Apoorva Mandavilli

  • Feb. 19, 2021Updated 11:49 a.m. ET

Nearly 30 million people in the United States — and probably many others whose illnesses were never diagnosed — have been infected with the coronavirus so far. Should these people still be vaccinated?

Two new studies answer that question with an emphatic yes.

In fact, the research suggests that for these people just one dose of the vaccine is enough to turbocharge their antibodies and destroy the coronavirus — and even some more infectious variants.

The results of these new studies are consistent with the findings of two others published over the past few weeks. Taken together, the research suggests that people who have had Covid-19 should be immunized — but a single dose of the vaccine may be enough.

“I think it’s a really strong rationale for why people who were previously infected with Covid should be getting the vaccine,” said Jennifer Gommerman, an immunologist at the University of Toronto who was not involved in the new research.

A person’s immune response to a natural infection is highly variable. Most people make copious amounts of antibodies that persist for many months. But some people who had mild symptoms or no symptoms of Covid-19 produce few antibodies, which quickly fall to undetectable levels.

The vaccines “even the playing field,” Dr. Gommerman said, so that anyone who has recovered from Covid-19 produces enough antibodies to protect against the virus.

The latest study, which has not yet been published in a scientific journal, analyzed blood samples from people who have had Covid-19. The findings suggested that their immune systems would have trouble fending off B.1.351, the coronavirus variant first identified in South Africa.

But one shot of either the Pfizer-BioNTech or Moderna vaccine significantly changed the picture: It amplified the amount of antibodies in their blood by a thousandfold — “a massive, massive boost,” said Andrew T. McGuire, an immunologist at the Fred Hutchinson Cancer Research Center in Seattle, who led the study.

Flush with antibodies, samples from all of the participants could neutralize not only B.1.351, but also the coronavirus that caused the SARS epidemic in 2003.

In fact, the antibodies seemed to perform better than those in people who had not had Covid and had received two doses of a vaccine. Multiple studies have suggested that the Pfizer-BioNTech and Moderna vaccines are about five times less effective against the variant.

A Covid-19 patient in the intensive care unit of Marian Regional Medical Center in Santa Maria, Calif., this month.
A Covid-19 patient in the intensive care unit of Marian Regional Medical Center in Santa Maria, Calif., this month.Credit…Daniel Dreifuss for The New York Times

The researchers obtained blood samples from 10 volunteers in the Seattle Covid Cohort Study who were vaccinated months after contracting the coronavirus. Seven of the participants received the Pfizer-BioNTech vaccine and three received the Moderna vaccine.

Blood taken about two to three weeks after vaccination showed a significant jump in the amounts of antibodies compared with the samples collected before vaccination. The researchers don’t yet know how long the increased amount of antibodies will persist, but “hopefully, they’ll last a long time,” Dr. McGuire said.

The researchers also saw increases in immune cells that remember and fight the virus, Dr. McGuire said. “It looks pretty clear that we’re boosting their pre-existing immunity,” he said.

In another new study, researchers at New York University found that a second dose of the vaccine did not add much benefit at all for people who have had Covid-19 — a phenomenon that has also been observed with vaccines for other viruses.

In that study, most people had been infected with the coronavirus eight or nine months earlier, but saw their antibodies increase by a hundredfold to a thousandfold when given the first dose of a vaccine. After the second dose, however, the antibody levels did not increase any further.

“It’s a real testament to the strength of the immunologic memory that they get a single dose and have a huge increase,” said Dr. Mark J. Mulligan, director of the N.Y.U. Langone Vaccine Center and the study’s lead author.

In some parts of the world, including the United States, a significant minority of the population has already been infected, Dr. Mulligan noted. “They definitely should be vaccinated,” he said.

It’s unclear whether the thousandfold spike in antibody levels recorded in the lab will occur in real-life settings. Still, the research shows that a single shot is enough to increase the levels of antibodies significantly, said Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York.

Dr. Krammer led another of the new studies, which showed that people who have had Covid-19 and received one dose of a vaccine experienced more severe side effects from the inoculation and had more antibodies compared with those who had not been infected before.

“If you put all four papers together, that’s providing pretty good information about people who already had an infection only needing one vaccination,” Dr. Krammer said.

He and other researchers are trying to persuade scientists at the Centers for Disease Control and Prevention to recommend only one dose for those who have recovered from Covid-19.

A woman receives a vaccine at a drive-through site in Hartford.Credit…Christopher Capozziello for The New York Times

Ideally, those people should be monitored after the first shot in case their antibody levels plummet after some weeks or months, said Dennis R. Burton, an immunologist at the Scripps Research Institute in La Jolla, Calif.

The fact that the supercharged antibodies observed in the new study can fight the 2003 SARS virus suggests that a single dose of the vaccine may have prompted the volunteers’ bodies to produce “broadly neutralizing antibodies” — immune molecules capable of attacking a broad range of related viruses, Dr. Burton said.

He and other scientists have for decades investigated whether broadly neutralizing antibodies can tackle multiple versions of H.I.V. at once. H.I.V. mutates faster than any other virus and quickly evades most antibodies.

The new coronavirus mutates much more slowly, but there are now multiple variants of the virus that seem to have evolved to be more contagious or to thwart the immune system. The new study may provide clues on how to make a single vaccine that stimulates the production of broadly neutralizing antibodies that can destroy all variants of the coronavirus, Dr. Burton said.

Without such a vaccine, scientists will need to tweak the vaccines every time the virus changes significantly. “You’re stuck in a kind of Whac-a-Mole approach,” he said. It will probably take many months if not longer to develop and test that sort of vaccine against the coronavirus, but “that’s the longer-term way to approach this virus.”

People Who Have Had Covid Should Get Single Vaccine Dose, Studies Suggest

People Who Have Had Covid Should Get Single Vaccine Dose, Studies Suggest

New studies show that one shot of a vaccine can greatly amplify antibody levels in those who have recovered from the coronavirus.

A nurse supervisor prepared a dose of the Pfizer-BioNTech vaccine at a mass vaccination site in Hartford, Conn., this month.
A nurse supervisor prepared a dose of the Pfizer-BioNTech vaccine at a mass vaccination site in Hartford, Conn., this month.Credit…Christopher Capozziello for The New York Times
Apoorva Mandavilli

  • Feb. 19, 2021, 9:49 a.m. ET

At least 30 million people in the United States — and probably many others whose illnesses were never diagnosed — have been infected with the coronavirus so far. Should these people still be vaccinated?

Two new studies answer that question with an emphatic yes.

In fact, the research suggests that for these people just one dose of the vaccine is enough to turbocharge their antibodies and destroy the coronavirus — and even some more infectious variants.

The results of these new studies are consistent with the findings of two others published over the past few weeks. Taken together, the research suggests that people who have had Covid-19 should be immunized — but a single dose of the vaccine may be enough.

“I think it’s a really strong rationale for why people who were previously infected with Covid should be getting the vaccine,” said Jennifer Gommerman, an immunologist at the University of Toronto who was not involved in the new research.

A person’s immune response to a natural infection is highly variable. Most people make copious amounts of antibodies that persist for many months. But some people who had mild symptoms or no symptoms of Covid-19 produce few antibodies, which quickly fall to undetectable levels.

The vaccines “even the playing field,” Dr. Gommerman said, so that anyone who has recovered from Covid-19 produces enough antibodies to protect against the virus.

The latest study, which has not yet been published in a scientific journal, analyzed blood samples from people who have had Covid-19. The findings suggested that their immune systems would have trouble fending off B.1.351, the coronavirus variant first identified in South Africa.

But one shot of either the Pfizer-BioNTech or Moderna vaccine significantly changed the picture: It amplified the amount of antibodies in their blood by a thousandfold — “a massive, massive boost,” said Andrew T. McGuire, an immunologist at the Fred Hutchinson Cancer Research Center in Seattle, who led the study.

Flush with antibodies, samples from all of the participants could neutralize not only B.1.351, but also the coronavirus that caused the SARS epidemic in 2003.

In fact, the antibodies seemed to perform better than those in people who had not had Covid and had received two doses of a vaccine. Multiple studies have suggested that the Pfizer-BioNTech and Moderna vaccines are about five times less effective against the variant.

A Covid-19 patient in the intensive care unit of Marian Regional Medical Center in Santa Maria, Calif., this month.
A Covid-19 patient in the intensive care unit of Marian Regional Medical Center in Santa Maria, Calif., this month.Credit…Daniel Dreifuss for The New York Times

The researchers obtained blood samples from 10 volunteers in the Seattle Covid Cohort Study who were vaccinated months after contracting the coronavirus. Seven of the participants received the Pfizer-BioNTech vaccine and three received the Moderna vaccine.

Blood taken about two to three weeks after vaccination showed a significant jump in the amounts of antibodies compared with the samples collected before vaccination. The researchers don’t yet know how long the increased amount of antibodies will persist, but “hopefully, they’ll last a long time,” Dr. McGuire said.

The researchers also saw increases in immune cells that remember and fight the virus, Dr. McGuire said. “It looks pretty clear that we’re boosting their pre-existing immunity,” he said.

In another new study, researchers at New York University found that a second dose of the vaccine did not add much benefit at all for people who have had Covid-19 — a phenomenon that has also been observed with vaccines for other viruses.

In that study, most people had been infected with the coronavirus eight or nine months earlier, but saw their antibodies increase by a hundredfold to a thousandfold when given the first dose of a vaccine. After the second dose, however, the antibody levels did not increase any further.

“It’s a real testament to the strength of the immunologic memory that they get a single dose and have a huge increase,” said Dr. Mark J. Mulligan, director of the N.Y.U. Langone Vaccine Center and the study’s lead author.

In some parts of the world, including the United States, a significant minority of the population has already been infected, Dr. Mulligan noted. “They definitely should be vaccinated,” he said.

It’s unclear whether the thousandfold spike in antibody levels recorded in the lab will occur in real-life settings. Still, the research shows that a single shot is enough to increase the levels of antibodies significantly, said Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York.

Dr. Krammer led another of the new studies, which showed that people who have had Covid-19 and received one dose of a vaccine experienced more severe side effects from the inoculation and had more antibodies compared with those who had not been infected before.

“If you put all four papers together, that’s providing pretty good information about people who already had an infection only needing one vaccination,” Dr. Krammer said.

He and other researchers are trying to persuade scientists at the Centers for Disease Control and Prevention to recommend only one dose for those who have recovered from Covid-19.

A woman receives a vaccine at a drive-through site in Hartford.Credit…Christopher Capozziello for The New York Times

Ideally, those people should be monitored after the first shot in case their antibody levels plummet after some weeks or months, said Dennis R. Burton, an immunologist at the Scripps Research Institute in La Jolla, Calif.

The fact that the supercharged antibodies observed in the new study can fight the 2003 SARS virus suggests that a single dose of the vaccine may have prompted the volunteers’ bodies to produce “broadly neutralizing antibodies” — immune molecules capable of attacking a broad range of related viruses, Dr. Burton said.

He and other scientists have for decades investigated whether broadly neutralizing antibodies can tackle multiple versions of H.I.V. at once. H.I.V. mutates faster than any other virus and quickly evades most antibodies.

The new coronavirus mutates much more slowly, but there are now multiple variants of the virus that seem to have evolved to be more contagious or to thwart the immune system. The new study may provide clues on how to make a single vaccine that stimulates the production of broadly neutralizing antibodies that can destroy all variants of the coronavirus, Dr. Burton said.

Without such a vaccine, scientists will need to tweak the vaccines every time the virus changes significantly. “You’re stuck in a kind of Whac-a-Mole approach,” he said. It will probably take many months if not longer to develop and test that sort of vaccine against the coronavirus, but “that’s the longer-term way to approach this virus.”

Childhood Colds Do Not Prevent Coronavirus Infection, Study Finds

Childhood Colds Do Not Prevent Coronavirus Infection, Study Finds

New research casts doubt on the idea that prior infections with garden-variety coronaviruses might shield some people, particularly children, amid the pandemic.

Drive-through coronavirus antibody testing last month in Los Angeles.
Drive-through coronavirus antibody testing last month in Los Angeles.Credit…Ringo Chiu/Agence France-Presse — Getty Images
Apoorva Mandavilli

  • Feb. 10, 2021, 5:00 a.m. ET

The theory was simple and compelling: Children are less vulnerable to the new coronavirus because they carry antibodies to other common coronaviruses that cause the common cold. The idea might also explain why some people infected with the new virus have mild symptoms while others — presumably without antibodies to common cold coronaviruses — are much more severely affected.

The notion gained traction particularly among people who claimed that this existing protection would swiftly bring human populations to herd immunity, the point at which a pathogen’s spread slows to a halt as it runs out of hosts to infect. A study in the journal Science, published in December, gave the hypothesis a strong boost.

But for all its appeal, the theory does not hold up, according to a new study published on Tuesday in the journal Cell. Based on carefully conducted experiments with live virus and with hundreds of blood samples drawn before and after the pandemic, the new research refutes the idea that antibodies to seasonal coronaviruses have any impact on the new coronavirus, called SARS-CoV-2.

“Going into this study, we thought we would learn that individuals that had pre-existing, pre-pandemic antibodies against SARS-CoV-2 would be less susceptible to infection and have less severe Covid-19 disease,” said Scott Hensley, an immunologist at the University of Pennsylvania. “That’s not what we found.”

He and his colleagues concluded that most people are exposed to seasonal coronaviruses by age 5. As a result, about one in five people carries antibodies that recognize the new coronavirus.

But these antibodies are not neutralizing — they cannot disarm the virus, nor do they mitigate the severity of symptoms following infection, the team found.

The researchers also compared antibodies to common cold coronaviruses in children and adults and found no difference in the amounts. By contrast, the study in Science had reported that about 5 percent of adults carried those antibodies, compared with 43 percent of children.

That study “reported very high levels of pre-pandemic cross-reactive neutralizing antibodies in kids, something that we did not find,” Dr. Hensley said. (“Cross-reactive” refers to antibodies able to attack similar sites on more than one type of virus.)

“I don’t have an explanation for the difference from the Science study, honestly,” he added.

Perhaps the difference in locations — Pennsylvania, in his study, versus Britain in the previous research — may explain some of the discrepancy, he said.

Other experts said they found Dr. Hensley’s study to be more convincing of the two and more consistent with circumstances in which large groups of people become infected with the new coronavirus.

Schoolchildren at the South Boston Catholic Academy in Boston gave themselves Covid-19 tests last month.
Schoolchildren at the South Boston Catholic Academy in Boston gave themselves Covid-19 tests last month.Credit…Allison Dinner/Reuters

For example, a single person infected with the new coronavirus at a Wisconsin summer camp set off an outbreak that affected 76 percent of the other attendees, noted John Moore, a virologist at Weill Cornell Medicine in New York.

Similarly, on a fishing trawler that left for sea from Seattle, only three sailors who had antibodies to the new coronavirus before the trip stayed virus-free. Those are not the infection rates you would see if protective antibodies were widely distributed in the population, Dr. Moore said.

“The idea that having the snuffles a while back somehow protects you from SARS-CoV-2 infection has always left me cold, but it’s been a persistent urban legend throughout the pandemic,” he said. “Hopefully, this new paper will finally cool everyone down and put such thoughts into the freezer.”

Experts also praised the new study’s careful and rigorous approach.

“It’s really nice to have a study that’s this well done,” said Shane Crotty, a virologist at the La Jolla Institute of Immunology in San Diego.

The theory that existing antibodies can protect people from the new virus “has definitely got a strong appeal because at first blush, it can explain a lot of the pandemic,” Dr. Crotty said. “But a beautiful idea doesn’t make it true.”

Dr. Hensley and his colleagues examined samples from 251 people who had donated blood to the University of Pennsylvania before the pandemic and then went on to develop Covid-19.

Those people carried levels of antibodies able to recognize the new coronavirus that were no different from those seen in blood samples drawn from 251 people who remained uninfected. And the levels showed no relationship to the clinical outcome in any of the patients.

“It’s hard to come by those kinds of samples — I was just impressed,” said Marion Pepper, an immunologist at the University of Washington in Seattle. “It’s like three different studies wrapped into one.”

The most important part of the coronavirus is the spike protein on its surface, which docks onto human cells. The spike is also the most distinctive part of the virus, so it makes sense that antibodies to seasonal viruses would be unlikely to recognize and disarm it, Dr. Pepper said.

“There are very specific parts of these viruses that are critical for infection, and most of this cross-reactivity isn’t directed to those parts,” she said.

But George Kassiotis, an immunologist at the Francis Crick Institute in London who led the study published in Science, disagreed with the conclusions of the new research. It “largely confirms rather than contradicts our main findings,” he said, adding that the new study was too small to rule out any role for existing antibodies.

But even if people really were carrying coronavirus antibodies from childhood infections, the protection they confer is not powerful enough to matter, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.

“If there is no effect that is measurable in a study with hundreds of people in both the infected and uninfected groups, then the effect is certainly tiny,” Dr. Bloom said.

Most of the vaccines developed for the new coronavirus are focused on the spike protein. Some scientists have argued that antibodies to other parts of the virus may also be critical to protection. But the new study suggests that the other antibodies are of minimal importance in protecting people from SARS-CoV-2.

The experts all said the new study did not rule out a role for immune cells, called memory B cells and T cells, produced in response to seasonal coronaviruses. Those cells might recognize some parts of the new virus and attack it, easing the severity of symptoms.

Still, the cells would not prevent infection, Dr. Crotty said. When exposed to the new virus, the immune cells might be roused “fast enough that you would have an asymptomatic infection that you never noticed,” he said. “But no, they wouldn’t stop infection.”

Tests of T cells are laborious and expensive, so analyses of their contribution to immunity are not yet complete. In the meantime, the new study at least rules out a significant role for existing antibodies, Dr. Hensley said: “We’ve sort of written one chapter here, but there’s still so much to be learned.”

Could a Single Vaccine Work Against All Coronaviruses?

Could a Single Vaccine Work Against All Coronaviruses?

Scientists are working on a shot that could protect against Covid-19, its variants, certain seasonal colds — and the next coronavirus pandemic.

Tara Gallion, a licensed practical nurse, prepared to administer doses of the Moderna Covid vaccine in Mound Bayou, Miss., last month.
Tara Gallion, a licensed practical nurse, prepared to administer doses of the Moderna Covid vaccine in Mound Bayou, Miss., last month.Credit…Rory Doyle for The New York Times
Carl Zimmer

  • Feb. 9, 2021, 11:26 a.m. ET

The invention of Covid-19 vaccines will be remembered as a milestone in the history of medicine, creating in a matter of months what had before taken up to a decade. But Dr. Kayvon Modjarrad, the director of Emerging Infectious Diseases Branch at Walter Reed Army Institute of Research in Silver Springs, Md., isn’t satisfied.

“That’s not fast enough,” he said. More than 2.3 million people around the world have died, and many countries will not have full access to the vaccines for another year or two: “Fast — truly fast — is having it there on day one.”

There will be more coronavirus outbreaks in the future. Bats and other mammals are rife with strains and species of this abundant family of viruses. Some of these pathogens will inevitably spill over the species barrier and cause new pandemics. It’s only a matter of time.

Dr. Modjarrad is one of many scientists who for years have been calling for a different kind of vaccine: one that could work against all coronaviruses. Those calls went largely ignored until Covid-19 demonstrated just how disastrous coronaviruses can be.

Now researchers are starting to develop prototypes of a so-called pancoronavirus vaccine, with some promising, if early, results from experiments on animals. Dr. Eric Topol, a professor of molecular medicine at the Scripps Research Institute in San Diego, thinks scientists should join together in another large-scale vaccine-creation project immediately.

“We have to get a real work force to accelerate this, so we can have it this year,” he said. Dr. Topol and Dennis Burton, a Scripps immunologist, called for this project on broad coronavirus vaccines on Monday in the journal Nature.

After coronaviruses were first identified in the 1960s, they did not become a high priority for vaccine makers. For decades it seemed as if they only caused mild colds. But in 2002, a new coronavirus called SARS-CoV emerged, causing a deadly pneumonia called severe acute respiratory syndrome, or SARS. Scientists scrambled to make a vaccine for it.

Dr. Kayvon Modjarrad, director of emerging infectious diseases at the Walter Reed Army Institute, during a coronavirus briefing in March.
Dr. Kayvon Modjarrad, director of emerging infectious diseases at the Walter Reed Army Institute, during a coronavirus briefing in March.Credit…Yasin Ozturk/Anadolu Agency, via Getty Images

Since no one had made a coronavirus vaccine for humans before, there was a huge amount to learn about its biology. Eventually, researchers chose a target for immunity: a protein on the surface of the virus, called spike. Antibodies that stick to the spike can prevent the coronavirus from entering cells and stop an infection.

Public health officials in Asia and elsewhere did not wait for the invention of a SARS vaccine to get to work, however. Their quarantines and other efforts proved remarkably effective. In a matter of months, they wiped out SARS-CoV, with only 774 deaths along the way.

The danger of coronaviruses became even clearer in 2012, when a second species spilled over from bats, causing yet another deadly respiratory disease called MERS. Researchers started work on MERS vaccines. But some researchers wondered if making a new vaccine for each new coronavirus — what Dr. Modjarrad calls “the one bug, one drug approach” — was the smartest strategy. Wouldn’t it be better, they thought, if a single vaccine could work against SARS, MERS and any other coronavirus?

That idea went nowhere for years. MERS and SARS caused relatively few deaths, and were soon eclipsed by outbreaks of other viruses such as Ebola and Zika.

In 2016, Maria Elena Bottazzi, a virologist at Baylor College of Medicine, and her colleagues applied for support from the American government to develop a pancoronavirus vaccine, but did not receive it. “They said there’s no interest in pancorona,” Dr. Bottazzi recalled.

Her team even lost funding for developing a SARS vaccine after they showed that it worked in mice, was not toxic to human cells and could be manufactured at scale. A coronavirus that had disappeared from view simply wasn’t a top priority.

Without enough money to start clinical trials, the scientists stored their SARS vaccine in a freezer and moved on to other research. “It’s been a struggle,” Dr. Bottazzi said.

Dr. Matthew Memoli, a virologist at the National Institute of Allergy and Infectious Diseases, looks back at those decisions as an enormous blunder. “It’s a failure of our system of science,” he said. “Funders tend to chase after shiny objects.”

A transmission electron micrograph of the Middle East Respiratory Syndrome.Credit…NIAID

Three years later, a third dangerous coronavirus emerged: the SARS-CoV-2 strain that causes Covid-19. Although this virus has a much lower fatality rate than its cousins that cause SARS and MERS, it does a far better job of spreading from person to person, resulting in more than 106 million documented cases around the world and still climbing.

All the lessons that researchers had learned about coronaviruses helped them move quickly to make new vaccines for SARS-CoV-2. Dr. Bottazzi and her colleagues used the technology they had created to make SARS vaccines to make one for Covid-19, which is now in early clinical trials.

Other researchers used even newer methods to move faster. The German company BioNTech created a genetic molecule called messenger RNA that encoded the spike protein. Partnering with Pfizer, the companies received U.S. government authorization for their vaccine in just 11 months. The previous record for a vaccine, against chickenpox, was four years.

Although the Covid-19 pandemic is still far from over, a number of researchers are calling for preparations for the next deadly coronavirus.

“This has already happened three times,” said Daniel Hoft, a virologist at Saint Louis University. “It’s very likely going to happen again.”

Researchers at VBI vaccines, a Cambridge-based company, took a small step toward a pancoronavirus vaccine last summer. They created virus-like shells studded with spike proteins from the three coronaviruses that caused SARS, MERS and Covid-19.

When the researchers injected this three-spike vaccine into mice, the animals made antibodies that worked against all three coronaviruses. Intriguingly, some of those antibodies could also latch onto a fourth human coronavirus that causes seasonal colds — even though that virus’s spike proteins were not included in the vaccine. The scientists have made this data public but have not yet published it in a scientific journal.

David Anderson, VBI’s chief scientific officer, said it was not clear why the vaccine worked this way. One possibility is that an immune cell presented with several versions of a protein at once doesn’t make antibodies against just one. Instead, it makes a compromise antibody that works against them all.

“You’re educating it,” Dr. Anderson said, although he cautioned that this was speculation for now.

Last month, Pamela Bjorkman, a structural biologist at Caltech, and her colleagues published a more extensive experiment with a universal coronavirus vaccine in the journal Science. The researchers attached only the tips of spike proteins from eight different coronaviruses to a protein core, known as a nanoparticle. After injecting these nanoparticles into mice, the animals generated antibodies that could stick to all eight of the coronaviruses — and to four other coronaviruses that the scientists had not used in the vaccine.

Sarah Clarke, a lab technician at the Sequencing and Genomic Technologies Shared Resource at Duke University, working with positive coronavirus samples.Credit…Pete Kiehart for The New York Times

Dr. Modjarrad is leading a team at Walter Reed developing another vaccine based on a nanoparticle studded with protein fragments. They anticipate starting clinical trials on volunteers next month. Although the vaccine currently uses protein fragments only from SARS-CoV-2 spikes, Dr. Modjarrad and his colleagues are preparing to retool it as a pancoronavirus vaccine.

Dr. Hoft of Saint Louis University is working on a universal vaccine that does not rely on antibodies to the spike protein. Collaborating with Gritstone Oncology, a California-based biotech company, he has created a vaccine that prompts cells to make surface proteins that might alert the immune system as if a coronavirus — any coronavirus — were present. They are now preparing a clinical trial to see if it is effective against SARS-CoV-2.

“We are interested to develop maybe a third-generation vaccine, which would be on the shelf and ready for the future outbreak,” Dr. Hoft said.

Dr. Topol believes scientists should also explore another strategy: searching for pancoronavirus antibodies made by our own bodies during infections.

Researchers studying H.I.V. and other viruses have discovered, amid the billions of antibodies made during an infection, rare types that work against a huge range of related strains. It might be possible to create vaccines that coax the body to make abundant amounts of these broadly neutralizing antibodies.

Coronaviruses are similar enough to each other, Dr. Topol said, that it might not be that hard to build vaccines that make broadly neutralizing antibodies. “This is an easy family of viruses to take down,” he said.

The search for a pancoronavirus vaccine may take longer than Dr. Topol’s sunny expectations. But even if it takes a few years, it could help prepare the world for the next coronavirus that jumps the species barrier.

“I think we can have vaccines to prevent pandemics like this,” Dr. Memoli said. “None of us wants to go through this again. And we don’t want our children to go through this again, or our grandchildren, or our descendants 100 years from now.”

Evidence Builds That Pregnant Women Pass Covid Antibodies to Newborns

Evidence Builds That Pregnant Women Pass Covid Antibodies to Newborns

A new study suggests that protective antibodies can be transferred through the placenta, and the baby may receive more of them if a mother is infected with Covid earlier in her pregnancy.

A woman  in McAllen, Tex., who tested positive for Covid-19 while she was pregnant. Studies suggest that pregnant women infected with the coronavirus can pass antibodies to their babies. 
A woman in McAllen, Tex., who tested positive for Covid-19 while she was pregnant. Studies suggest that pregnant women infected with the coronavirus can pass antibodies to their babies. Credit…Carolyn Cole/Getty Images
Christina Caron

  • Jan. 29, 2021, 9:04 p.m. ET

One of the many big questions scientists are trying to untangle is whether people who get Covid-19 during pregnancy will pass on some natural immunity to their newborns.

Recent studies have hinted that they might. And new findings, published Friday in the journal JAMA Pediatrics, provide another piece of the puzzle, offering more evidence that Covid-19 antibodies can cross the placenta.

“What we have found is fairly consistent with what we have learned from studies of other viruses,” said Scott E. Hensley, an associate professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania and one of the senior authors of the study.

Additionally, he added, the study suggests that women are not only transferring antibodies to their fetuses, but also transferring more antibodies to their babies if they are infected earlier in their pregnancies. This might have implications for when women should be vaccinated against Covid-19, Dr. Hensley said, adding that vaccinating women earlier in pregnancy might offer more protective benefits, “but studies actually analyzing vaccination among pregnant women need to be completed.”

In the study, researchers from Pennsylvania tested more than 1,500 women who gave birth at Pennsylvania Hospital in Philadelphia between April and August of last year. Of those, 83 women were found to have Covid-19 antibodies — and after they gave birth, 72 of those babies tested positive for Covid-19 antibodies via their cord blood, regardless of whether their mothers had symptoms.

According to Dr. Karen Puopolo, an associate professor of pediatrics at the University of Pennsylvania and one of the senior authors of the study, about half of those babies had antibody levels that were as high or higher than those found in their mother’s blood, and in about a quarter of the cases, the antibody levels in the cord blood was 1.5 to 2 times higher than the mother’s concentrations.

“That’s fairly efficient,” Dr. Puopolo said.

The researchers also observed that the longer the time period between the start of a pregnant woman’s Covid-19 infection and her delivery, the more antibodies were transferred, a finding that has been noted elsewhere.

The antibodies that crossed the placenta were immunoglobulin G, or IgG, antibodies, the type that are made days after getting infected and are thought to offer long-term protection against the coronavirus.

None of the babies in this study were found to have immunoglobulin M, or IgM, antibodies, which are typically only detected soon after an infection, suggesting that the babies hadn’t been infected with the coronavirus.

Experts don’t yet know if the amount of antibodies that passed on to the babies were enough to prevent newborns from getting Covid-19. And because only a few of the babies in the study were born prematurely, the researchers can’t say whether babies who are born early might miss out on those protective antibodies. The study authors also noted that because their results were from just one facility, the findings would need to be further replicated.

The placenta is a complex organ, and one that has been understudied, said Dr. Denise Jamieson, an obstetrician at Emory University in Atlanta and a member of the Covid expert group at the American College of Obstetricians and Gynecologists, who was not involved with the study.

And more research is needed to better understand whether vaccine-generated antibodies behave comparably to antibodies from Covid-19 infection, said Dr. Andrea G. Edlow, an assistant professor of obstetrics, gynecology and reproductive biology at Harvard Medical School.

In a study published in the journal Cell in December, for instance, Dr. Edlow and her colleagues found that Covid-19 antibodies from a natural infection might cross the placenta less efficiently than the antibodies produced after vaccination for flu and whooping cough (pertussis).

“What we really want to know is, do antibodies from the vaccine efficiently cross the placenta and protect the baby, the way we know happens in influenza and pertussis,” Dr. Jamieson said.

Experts do not know whether the Covid vaccine will work in this way, in part because pregnant women were excluded from the initial clinical trials.

“It’s plausible that the Covid vaccine will offer protection to both pregnant mothers and their infants,” said Dr. Mark Turrentine, a member of the Covid expert group at A.C.O.G. “To me,” he added, “this study highlights that inclusion of pregnant women in clinical trials such as the Covid-19 vaccine is essential, particularly when the benefit of vaccination is greater than the potential risk of a life-threatening disease.”

How the Coronavirus Turns the Body Against Itself

How the Coronavirus Turns the Body Against Itself

Some patients struggling with Covid-19 develop antibodies against their own tissues, scientists have found.

A Covid-19 patient at Sharp Grossmont Hospital in La Mesa, Calif., this month. Some patients produce antibodies similar to those produced in more familiar diseases, like lupus. 
A Covid-19 patient at Sharp Grossmont Hospital in La Mesa, Calif., this month. Some patients produce antibodies similar to those produced in more familiar diseases, like lupus. Credit…Etienne Laurent/EPA, via Shutterstock
Apoorva Mandavilli

  • Jan. 28, 2021, 5:00 a.m. ET

The coronavirus can warp the body’s defenses in many ways — disarming the body’s early warning systems, for example, or causing immune cells to misfire. But a spate of new studies suggests another insidious consequence: The infection can trigger the production of antibodies that mistakenly attack the patient’s own tissues instead of the virus.

The latest report, published online this week, suggests that so-called autoantibodies can persist months after the infection has resolved, perhaps causing irreparable harm. If other studies confirm the finding, it may explain some of the lingering symptoms in people who have recovered from Covid-19. The syndrome, sometimes referred to as long Covid, can include dementia, “brain fog” and joint pain.

Autoantibodies are not new to science: They are the misguided soldiers of the immune system, tied to debilitating diseases such as lupus and rheumatoid arthritis, which arise when the body attacks its own tissues.

The newest study is small, with just nine patients, five of whom had autoantibodies for at least seven months. It has not yet undergone peer review for publication, and the authors urged caution in interpreting the results.

“It’s a signal; it is not definitive,” said Dr. Nahid Bhadelia, medical director of the special pathogens unit at Boston Medical Center, who led the study. “We don’t know how prevalent it is, and whether or not it can be linked to long Covid.”

The question of autoimmunity following coronavirus infection is urgent and important, Dr. Bhadelia added. As many as one in three survivors of Covid-19 say they still experience symptoms.

“This is a real phenomenon,” she said. “We’re looking at a second pandemic of people with ongoing potential disability who may not be able to return to work, and that’s a huge impact on the health systems.”

A growing body of evidence suggests that autoimmunity contributes to the severity of Covid-19 in some people. A study published online in October found that among 52 patients with severe Covid-19, more than 70 percent carried antibodies against their own DNA and against proteins that help with blood clotting.

In another study, also published online in October, researchers discovered autoantibodies to carbohydrates made by the body in Covid-19 patients, which could explain neurological symptoms. And a study in the journal Science Translational Medicine in November found that half of patients hospitalized for Covid-19 had at least transient autoantibodies that cause clots and blockages in blood vessels.

The gathering research raises the worrying possibility that lingering autoantibodies might lead to autoimmune disease in some people infected with the coronavirus.

“Once these autoantibodies are induced, there is no going back,” said Akiko Iwasaki, an immunologist at Yale University. “They will be a permanent part of the person’s immune system.”

She added: “What does it do to vaccine response? What does it do to newly acquired infections? These are all questions that will have to be addressed.”

Dr. Iwasaki’s team showed in December that severely ill patients had dramatic increases in a wide array of autoantibodies that target parts of the immune system, brain cells, connective tissue and clotting factors.

“We really see broadly reactive autoantibody responses in these patients,” Dr. Iwasaki said. She had suspected that autoimmunity might play some role, but “even I didn’t expect to see this much auto-reactivity.”

A colorized scanning electron micrograph of a cell (blue) heavily infected with coronavirus particles, isolated from a patient sample in December.
A colorized scanning electron micrograph of a cell (blue) heavily infected with coronavirus particles, isolated from a patient sample in December.Credit…NIAID/National Institutes of Health, via EPA, Shutterstock

Dr. Iwasaki and her colleagues collected blood from 172 patients with a range of symptoms, 22 health care workers who had been infected, and 30 uninfected health care workers.

One in five infected patients had autoantibodies to five proteins in their own bodies, and up to 80 percent to at least one protein, the researchers found. Patients with severe Covid-19 had many more of these antibodies, which hindered their immune responses and exacerbated illness. Of 15 patients who died during the study, 14 had autoantibodies to at least one constituent of the immune system.

The study convincingly shows that autoantibodies “alter the course of disease,” said Marion Pepper, an immunologist at the University of Washington in Seattle who was not involved in the research.

Autoimmunity after an illness is not unique to the coronavirus. Other intensely inflammatory infections, including malaria, leprosy and respiratory viruses, are also known to trigger autoantibodies. But autoimmunity and Covid-19 may be a particularly hazardous mix, experts said.

One analysis of nearly 170,000 people with rare autoimmune rheumatic diseases like lupus and scleroderma indicated that they face increased odds of death from Covid-19. And a study of more than 130,000 people found that autoimmune conditions like Type 1 diabetes, psoriasis and rheumatoid arthritis increase the risk of respiratory complications and death from Covid-19.

Some of the antibodies seemed to be the result of inborn defects in the immune system. For example, a study in the journal Science in October found that about 10 percent of severely ill Covid-19 patients had existing autoantibodies that attacked key components of the immune system that were supposed to kick in after exposure to the virus. Without that rapid response, the body’s defense is hopelessly delayed, fighting a losing battle against the multiplying virus.

Yet the mere presence of autoantibodies does not indicate harm. They are in the general population and don’t always lead to illness, some experts noted.

“Anywhere from 10 to 15 percent of the population has some level of this auto-reactivity,” said Dr. Iñaki Sanz, an immunologist at Emory University. “The issue is that you need many other events downstream of the autoantibodies to induce disease.”

At least in some patients, autoantibodies clearly emerged as a result of the illness, Dr. Iwasaki’s study showed. Extreme inflammation caused by viral infections can cause cells to burst open, spewing their contents and befuddling the immune system’s ability to distinguish “self” from “other.”

But autoantibodies induced in this manner may level off after a few months, said Dr. Shiv Pillai, an immunologist at Harvard University: “Probably in the vast majority of Covid-19 patients, autoantibodies emerge in the acute phase, then decline.”

“That being said — yes, it would be interesting if long Covid might be explained by specific autoantibodies,” he added.

Several researchers, including Dr. Bhadelia and Dr. Iwasaki, are following patients over time to see how long autoantibodies persist and whether they wreak permanent damage. Although scientists have known that acute infections can trigger their presence, the phenomenon has never been studied in such detail.

“That’s maybe the one silver lining here,” Dr. Pepper said. “We’re going to learn some fundamental principles about acute viral infections in people which haven’t been easy to study in this way before.”

Emerging Coronavirus Variants May Pose Challenges to Vaccines

Emerging Coronavirus Variants May Pose Challenges to Vaccines

Laboratory studies of mutations circulating in South Africa suggest they may dodge some of the body’s immune responses.

Health workers tended to a Covid-19 patient at Greenacres Hospital in Port Elizabeth, South Africa, in November.
Health workers tended to a Covid-19 patient at Greenacres Hospital in Port Elizabeth, South Africa, in November.Credit…Samantha Reinders for The New York Times
Apoorva Mandavilli

  • Jan. 20, 2021, 6:37 p.m. ET

The steady drumbeat of reports about new variants of the coronavirus — first in Britain, then in South Africa, Brazil and the United States — have brought a new worry: Will vaccines protect against these altered versions of the virus?

The answer so far is yes, several experts said in interviews. But two small new studies, posted online Tuesday night, suggest that some variants may pose unexpected challenges to the immune system, even in those who have been vaccinated — a development that most scientists had not anticipated seeing for months, even years.

The findings result from laboratory experiments with blood samples from groups of patients, not observations of the virus spreading in the real world. The studies have not yet been peer-reviewed.

But experts who reviewed the papers agreed that the findings raised two disturbing possibilities. People who had survived mild infections with the coronavirus may still be vulnerable to infection with a new variant; and more worryingly, the vaccines may be less effective against the variants.

Existing vaccines will still prevent serious illness, and people should continue getting them, said Dr. Michel Nussenzweig, an immunologist at Rockefeller University in New York, who led one of the studies: “If your goal is to keep people out of the hospital, then this is going to work just fine.”

But the vaccines may not prevent people from becoming mildly or asymptomatically infected with the variants, he said. “They may not even know that they were infected,” Dr. Nussenzweig added. If the infected can still transmit the virus to others who are not immunized, it will continue to claim lives.

The vaccines work by stimulating the body to produce antibodies against the coronavirus. Scientists had expected that over time, the virus may gain mutations that allow it to evade these antibodies — so-called escape mutations. Some studies had even predicted which mutations would be most advantageous to the virus.

But scientists had hoped that the new vaccines would remain effective for years, on the theory that the coronavirus would be slow to develop new defenses against them. Now some researchers fear the unchecked spread has given the virus nearly unfettered opportunities to reinvent itself, and may have hastened the appearance of escape mutations.

The studies published on Tuesday night show that the variant identified in South Africa is less susceptible to the antibodies created by natural infection and by vaccines made by Pfizer-BioNTech and Moderna.

Vaccinations of nurses, doctors and health professionals in São Paulo, Brazil, this week.
Vaccinations of nurses, doctors and health professionals in São Paulo, Brazil, this week.Credit…Victor Moriyama for The New York Times

Neither the South African variant nor a similar mutant virus in Brazil has yet been detected in the United States. (The more contagious variant that has blazed through Britain does not contain these mutations and seems to be susceptible to vaccines.)

Fears that the vaccines would be powerless against new variants intensified at a scientific conference held online on Saturday, when South African scientists reported that in laboratory tests, serum samples from 21 of a group of 44 Covid-19 survivors did not destroy the variant circulating in that country.

The samples that were successful against the variant were taken from patients who had been hospitalized. These patients had higher blood levels of so-called neutralizing antibodies — the subset of antibodies needed to disarm the virus and prevent infection — than those who were only mildly ill.

The results “strongly, strongly suggest that several mutations that we see in the South Africa variant are going to have a significant effect on the sensitivity of that virus to neutralization,” said Penny Moore, a virologist at the National Institute for Communicable Diseases in South Africa who led the study.

The second study brought better tidings, at least about vaccines.

In that study, Dr. Nussenzweig and his colleagues tested samples from 14 people who had received the Moderna vaccine and six people who had received the Pfizer-BioNTech vaccine.


Covid-19 Vaccines ›


Answers to Your Vaccine Questions

While the exact order of vaccine recipients may vary by state, most will likely put medical workers and residents of long-term care facilities first. If you want to understand how this decision is getting made, this article will help.

Life will return to normal only when society as a whole gains enough protection against the coronavirus. Once countries authorize a vaccine, they’ll only be able to vaccinate a few percent of their citizens at most in the first couple months. The unvaccinated majority will still remain vulnerable to getting infected. A growing number of coronavirus vaccines are showing robust protection against becoming sick. But it’s also possible for people to spread the virus without even knowing they’re infected because they experience only mild symptoms or none at all. Scientists don’t yet know if the vaccines also block the transmission of the coronavirus. So for the time being, even vaccinated people will need to wear masks, avoid indoor crowds, and so on. Once enough people get vaccinated, it will become very difficult for the coronavirus to find vulnerable people to infect. Depending on how quickly we as a society achieve that goal, life might start approaching something like normal by the fall 2021.

Yes, but not forever. The two vaccines that will potentially get authorized this month clearly protect people from getting sick with Covid-19. But the clinical trials that delivered these results were not designed to determine whether vaccinated people could still spread the coronavirus without developing symptoms. That remains a possibility. We know that people who are naturally infected by the coronavirus can spread it while they’re not experiencing any cough or other symptoms. Researchers will be intensely studying this question as the vaccines roll out. In the meantime, even vaccinated people will need to think of themselves as possible spreaders.

The Pfizer and BioNTech vaccine is delivered as a shot in the arm, like other typical vaccines. The injection won’t be any different from ones you’ve gotten before. Tens of thousands of people have already received the vaccines, and none of them have reported any serious health problems. But some of them have felt short-lived discomfort, including aches and flu-like symptoms that typically last a day. It’s possible that people may need to plan to take a day off work or school after the second shot. While these experiences aren’t pleasant, they are a good sign: they are the result of your own immune system encountering the vaccine and mounting a potent response that will provide long-lasting immunity.

No. The vaccines from Moderna and Pfizer use a genetic molecule to prime the immune system. That molecule, known as mRNA, is eventually destroyed by the body. The mRNA is packaged in an oily bubble that can fuse to a cell, allowing the molecule to slip in. The cell uses the mRNA to make proteins from the coronavirus, which can stimulate the immune system. At any moment, each of our cells may contain hundreds of thousands of mRNA molecules, which they produce in order to make proteins of their own. Once those proteins are made, our cells then shred the mRNA with special enzymes. The mRNA molecules our cells make can only survive a matter of minutes. The mRNA in vaccines is engineered to withstand the cell’s enzymes a bit longer, so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.

The researchers saw a slight decrease in antibody activity directed against engineered viruses with three of the key mutations in the variant identified in South Africa. That result was significant “because it’s seen in just about every individual tested,” Dr. Nussenzweig said. Still, it “is not something that we should be horribly freaked out about.”

In most people, infection with the coronavirus leads to a strong immune response; the vaccines seem to induce an even more powerful response. Two doses of the vaccines from Pfizer and Moderna, at least, produce neutralizing antibodies at levels that are higher than those acquired through natural infection.

Even if antibody effectiveness were reduced tenfold, the vaccines would still be quite effective against the virus, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.

In Liverpool, England, people lined up to receive a coronavirus test at a recreational tennis center last year.Credit…Mary Turner for The New York Times

And while neutralizing antibodies are essential for preventing infection, the vaccines — and natural infection — also lead to production of thousands of other types of antibodies, not to mention various immune cells that retain a memory of the virus and can be roused to action when the body encounters it again.

Even when confronted with variants, those other components of the immune system may be enough to prevent serious illness, said Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York. In clinical trials, the vaccines protected people from illness after just one dose, when the levels of neutralizing antibodies were low or undetectable, he noted.

Vaccine trials being conducted in South Africa by Novavax and Johnson & Johnson will provide more real-world data on how the vaccines perform against the new variant there. Those results are expected within the next few weeks.

All viruses mutate, and it’s no surprise that some of those mutations sidestep the body’s immune defenses, experts said. Each new host affords a virus fresh opportunities to amass and test mutations by slightly scrambling the sequence of RNA letters in its genetic code.

“The beauty, the elegance, the evolution and the magnificence of a virus is that every single time it infects a person, it’s exploring that sequence space,” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh.

Some mutations don’t improve on the original, and fade away. Others add to the pathogen’s power, by making it more contagious — like the variant first identified in Britain — more fit, or less susceptible to immunity.

The mutations in the variant circulating in South Africa, called B.1.351, have independently emerged more than once, and all together, suggesting that they work in concert to benefit the virus.

A field hospital for treating Covid-19 patients outside Port Elizabeth, South Africa, in November. Credit…Samantha Reinders for The New York Times

The key mutation, called E484K, and two of its companions alter the shape of a part of the virus that is crucial for immune recognition, making it difficult for antibodies to attach themselves to the virus. The trio popped up in several lab studies that tried to predict which mutations would be advantageous to the virus.

“I think we need to monitor mutations closely and look out for things like that that could be becoming dominant in certain parts of the world,” said Akiko Iwasaki, an immunologist at Yale University.

Britain detected the more contagious variant circulating there because it sequences more virus samples than any other nation. The United States lags far behind: It has sequenced about 71,000 samples so far, a tiny proportion of the millions infected in the country. But the Centers for Disease Control and Prevention plans to work with state and local public health labs to sequence as many as 6,000 samples per week, agency scientists said Friday.

It will be important to limit travel — and the import of variants — from other countries until a majority of the population is immunized, said John Moore, a virologist at Weill Cornell Medicine in New York.

“Even if they are already here, the more often they are reintroduced, the more likely there could be a super-spreader event,” Dr. Moore said. (President Joseph R. Biden Jr. plans to sustain existing travel restrictions on anyone who has recently traveled to Europe and Brazil.)

The mRNA technology on which the Pfizer and Moderna vaccines rely can be altered in a matter of weeks, and far more easily than the process used to produce flu vaccines. But it would be wise to prepare for this eventuality now and think through not just the technical aspects of updating the vaccines, but the testing, approval and rollout of those vaccines, experts said.

Still, the best path forward is to prevent the emergence of new mutations and variants altogether, they said.

“Imagine having to do catch-up like this all the time — it’s not something desirable,” Dr. Iwasaki said. “If we can just stop the spread as soon as possible, while the vaccine is very effective, that’s the best way.”