Recipients of the Moderna and the J.&J. vaccines may receive extra doses, the committee said, although the shots continue to prevent illness and death.
Tag: Immune System
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Moderna vs. Pfizer: Both Knockouts, but One Seems to Have the Edge
Breakthrough Infections and the Delta Variant: What to Know
What to Know About Breakthrough Infections and the Delta Variant
Behind the Masks, a Mystery: How Often Do the Vaccinated Spread the Virus?
Why Everyone Has the Worst Summer Cold Ever
You’re Missing Microbes. But Is ‘Rewilding’ the Way to Get Them Back?
Covid Is Especially Risky for People With H.I.V., Large Study Finds
Delta Variant Widens Gulf Between ‘Two Americas’: Vaccinated and Unvaccinated
Should People With Immune Problems Get Third Vaccine Doses?
Johnson & Johnson Vaccine Protects Against Delta Variant, Company Reports
How the ‘Alpha’ Coronavirus Variant Became So Powerful
A new study suggests how the variant first identified in Britain hides from the human immune system. Its stealth may be part of its success.
In December, British researchers discovered that a new variant was sweeping through their country. When it arrived in other countries, the variant, now known as Alpha, tended to become more common in its new homes as well. By April, it had become the dominant variant in the United States, and it has remained so ever since.
Alpha’s swift success has left scientists wondering how the variant conquered the world. A new study points to one secret to its success: Alpha disables the first line of immune defense in our bodies, giving the variant more time to multiply.
“It’s very impressive,” said Dr. Maudry Laurent-Rolle, a physician and virologist at the Yale School of Medicine who was not involved in the new study. “Any successful virus has to get beyond that first defense system. The more successful it is at doing that, the better off the virus is.”
The report was posted online on Monday and has not yet been published in a scientific journal.
Alpha has 23 mutations that set it apart from other coronaviruses. When the variant started to surge in Britain, researchers began inspecting these genetic tweaks to look for explanations as to why it was spreading faster than other variants.
A lot of researchers focused their attention on the nine mutations that alter the so-called spike protein that covers the coronavirus and allows it to invade cells. One of those mutations helps the virus bind more tightly to cells, potentially improving its chances of a successful infection.
But other scientists have focused on how Alpha affects the human immune response. Gregory Towers, a virologist at the University College London, and his colleagues grew coronaviruses in human lung cells, comparing Alpha-infected cells with those infected with earlier variants of the coronavirus.
They found that lung cells with Alpha made drastically less interferon, a protein that switches on a host of immune defenses. They also found that in the Alpha cells, the defensive genes normally switched on by interferon were quieter than in cells infected with other variants.
Somehow, the immune system’s most important alarm bells were barely ringing in the presence of the Alpha variant. “It’s making itself more invisible,” Dr. Towers said.
To investigate how Alpha achieved this invisibility, the researchers looked at how the coronavirus replicated inside of infected cells. They found that Alpha-infected cells make a lot of extra copies — some 80 times more than other versions of the virus — of a gene called Orf9b.
“It’s off the chart,” said Nevan Krogan, a molecular biologist at the University of California, San Francisco, and a co-author of the new study.
In previous research, Dr. Krogan and his colleagues had found that Orf9b makes a viral protein that locks onto a human protein called Tom70. And it just so happens that Tom70 is essential for a cell’s release of interferon in the face of an invading virus.
Putting all of the evidence together, Dr. Krogan and his colleagues argue that the Alpha variant carries a mutation that forces the production of a lot more Orf9b proteins. Those proteins swarm the human Tom70 proteins, dampening the production of interferon and a full immune response. The virus, protected from attack, has better odds of making copies of itself.
An infected cell can gradually remove the Orf9b proteins from its Tom70 molecules, however. By about 12 hours after infection, the alarm system starts coming back online. And because of that immune response, Dr. Towers said, “all hell breaks loose.”
Dr. Towers speculated that when the delayed immune response finally happens, people infected with Alpha have a more robust reaction than they would with other variants, coughing and shedding virus-laden mucus from not only their mouths, but also their noses — making Alpha even better at spreading.
“What they’re showing makes sense,” Dr. Laurent-Rolle said. But she would like to see more lines of evidence in support of their conclusion. For example, the scientists did not run a standard test to measure the number of Orf9b proteins.
“That’s one thing that could be concerning,” she said. Dr. Krogan said he and his colleagues were developing that test now.
Dr. Krogan’s team has also started similar experiments on other variants, including the variant first identified in South Africa, known as Beta, and the one first identified in India, known as Delta. The preliminary results surprised them.
Both Beta and Delta drive down interferon in infected cells. But there’s no sign that they do so by flooding the cells with Orf9b proteins. They may have independently evolved their own tricks for manipulating our immune system.
“They’re all turning down the immune response in different ways,” Dr. Krogan said.
Cecile King, an immunologist at the Garvan Institute of Medical Research in Sydney, Australia, who was not involved in the study, said that understanding how the virus was evolving these escapes would help scientists design better vaccines for Covid-19.
The current crop of vaccines direct the immune system to recognize spike proteins. But studies on people who recover naturally from Covid-19 have shown that their immune systems learn to recognize other viral proteins, including Orf9b.
A number of researchers are putting together combinations of coronavirus proteins into new vaccines. But they need to take caution, because some of the proteins may actually dampen immunity.
“It’s quite a tricky enterprise, but becoming more possible as we learn more,” Dr. King said.
Immunity to the Coronavirus May Persist for Years, Scientists Find
Important immune cells survive in the bone marrow of people who were infected with the virus or were inoculated against it, new research suggests.
Immunity to the coronavirus lasts at least a year, probably much longer, and improves over time especially after vaccination, according to two new studies. The findings may help put to rest lingering fears that protection against the virus will be short-lived.
Together, the studies suggest that most people who have recovered from Covid-19 and who were later immunized will not need boosters. Vaccinated people who were never infected most likely will need the shots, however, as will a minority who were infected but did not produce a robust immune response.
Both reports looked at people who had been exposed to the coronavirus about a year earlier. Cells that retain a memory of the virus persist in the bone marrow and may churn out antibodies whenever needed, according to one of the studies, published on Monday in the journal Nature.
The other study, which is also under review for publication in Nature, found that these so-called memory B cells continue to mature and strengthen for at least 12 months after the initial infection.
“The papers are consistent with the growing body of literature that suggests that immunity elicited by infection and vaccination for SARS-CoV-2 appears to be long-lived,” said Scott Hensley, an immunologist at the University of Pennsylvania who was not involved in the research.
The studies may soothe fears that immunity to the virus is transient, as is the case with coronaviruses that cause common colds. But those viruses change significantly every few years, Dr. Hensley said. “The reason we get infected with common coronaviruses repetitively throughout life might have much more to do with variation of these viruses rather than immunity,” he said.
In fact, memory B cells produced in response to infection with SARS-CoV-2 and enhanced with vaccination are so potent that they thwart even variants of the virus, negating the need for boosters, according to Michel Nussenzweig, an immunologist at Rockefeller University in New York who led the study on memory maturation.
“People who were infected and get vaccinated really have a terrific response, a terrific set of antibodies, because they continue to evolve their antibodies,” Dr. Nussenzweig said. “I expect that they will last for a long time.”
The result may not apply to protection derived from vaccines alone, because immune memory is likely to be organized differently after immunization, compared with that following natural infection.
That means people who have not had Covid-19 and have been immunized may eventually need a booster shot, Dr. Nussenzweig said. “That’s the kind of thing that we will know very, very soon,” he said.
Upon first encountering a virus, B cells rapidly proliferate and produce antibodies in large amounts. Once the acute infection is resolved, a small number of the cells take up residence in the bone marrow, steadily pumping out modest levels of antibodies.
To look at memory B cells specific to the new coronavirus, researchers led by Ali Ellebedy of Washington University in St. Louis analyzed blood from 77 people at three-month intervals, starting about a month after their infection with the coronavirus. Only six of the 77 had been hospitalized for Covid-19; the rest had mild symptoms.
Antibody levels in these individuals dropped rapidly four months after infection and continued to decline slowly for months afterward — results that are in line with those from other studies.
Some scientists have interpreted this decrease as a sign of waning immunity, but it is exactly what’s expected, other experts said. If blood contained high quantities of antibodies to every pathogen the body had ever encountered, it would quickly transform into a thick sludge.
Instead, blood levels of antibodies fall sharply following acute infection, while memory B cells remain quiescent in the bone marrow, ready to take action when needed.
Dr. Ellebedy’s team obtained bone marrow samples from 19 people roughly seven months after they had been infected. Fifteen had detectable memory B cells, but four did not, suggesting that some people might carry very few of the cells or none at all.
“It tells me that even if you got infected, it doesn’t mean that you have a super immune response,” Dr. Ellebedy said. The findings reinforce the idea that people who have recovered from Covid-19 should be vaccinated, he said.
Five of the participants in Dr. Ellebedy’s study donated bone marrow samples seven or eight months after they were initially infected and again four months later. He and his colleagues found that the number of memory B cells remained stable over that time.
The results are particularly noteworthy because it is difficult to get bone marrow samples, said Jennifer Gommerman, an immunologist at the University of Toronto who was not involved in the work.
A landmark study in 2007 showed that antibodies in theory could survive decades, perhaps even well beyond the average life span, hinting at the long-term presence of memory B cells. But the new study offered a rare proof of their existence, Dr. Gommerman said.
Dr. Nussenzweig’s team looked at how memory B cells mature over time. The researchers analyzed blood from 63 people who had recovered from Covid-19 about a year earlier. The vast majority of the participants had mild symptoms, and 26 had also received at least one dose of either the Moderna or the Pfizer-BioNTech vaccine.
So-called neutralizing antibodies, needed to prevent reinfection with the virus, remained unchanged between six and 12 months, while related but less important antibodies slowly disappeared, the team found.
As memory B cells continued to evolve, the antibodies they produced developed the ability to neutralize an even broader group of variants. This ongoing maturation may result from a small piece of the virus that is sequestered by the immune system — for target practice, so to speak.
A year after infection, neutralizing activity in the participants who had not been vaccinated was lower against all forms of the virus, with the greatest loss seen against the variant first identified in South Africa.
Vaccination significantly amplified antibody levels, confirming results from other studies; the shots also ramped up the body’s neutralizing ability by about 50-fold.
Senator Rand Paul, Republican of Kentucky, said on Sunday that he would not get a coronavirus vaccine because he had been infected in March of last year and was therefore immune.
But there is no guarantee that such immunity will be powerful enough to protect him for years, particularly given the emergence of variants of the coronavirus that can partially sidestep the body’s defenses.
The results of Dr. Nussenzweig’s study suggest that people who have recovered from Covid-19 and who have later been vaccinated will continue to have extremely high levels of protection against emerging variants, even without receiving a vaccine booster down the line.
“It kind of looks exactly like what we would hope a good memory B cell response would look like,” said Marion Pepper, an immunologist at the University of Washington in Seattle who was not involved in the new research.
The experts all agreed that immunity is likely to play out very differently in people who have never had Covid-19. Fighting a live virus is different from responding to a single viral protein introduced by a vaccine. And in those who had Covid-19, the initial immune response had time to mature over six to 12 months before being challenged by the vaccine.
“Those kinetics are different than someone who got immunized and then gets immunized again three weeks later,” Dr. Pepper said. “That’s not to say that they might not have as broad a response, but it could be very different.”
Covid Vaccines Protect Pregnant Women, Study Confirms
The shots may also have benefits for infants and do not seem to damage the placenta, according to the latest research.
When the coronavirus vaccines were first authorized in December, scientists knew little about how well they might work in pregnant women, who had been excluded from the clinical trials.
Since then, scientists have accumulated a small but steadily growing body of evidence that the vaccines are safe and effective during pregnancy. Preliminary results from two continuing studies provide additional encouraging news.
The Pfizer-BioNTech and Moderna vaccines produce robust immune responses in pregnant and lactating women, and are likely to provide at least some protection against two dangerous coronavirus variants, according to a study published in JAMA on Thursday. Vaccinated women can also pass protective antibodies to their fetuses through the bloodstream and to their infants through breast milk, the research suggests.
In a second study, published in the journal Obstetrics & Gynecology on Tuesday, researchers found no evidence that either the Pfizer or Moderna vaccines damaged the placenta during pregnancy.
“We can shift our framework from, ‘Let’s protect pregnant people from the vaccine,’ to ‘Let’s protect pregnant people and their infants through the vaccine,’” said Dr. Emily S. Miller, an expert in maternal-fetal medicine at Northwestern University and co-author of the placenta study. “I think that’s really powerful.”
Covid presents serious risks during pregnancy. Research has shown, for instance, that pregnant women with coronavirus symptoms are more likely to be admitted to the intensive care unit, require mechanical ventilation and to die from the virus than are symptomatic women of a similar age who are not pregnant.
Because of these risks, the Centers for Disease Control and Prevention has recommended that the vaccines at least be made available to pregnant people, many of whom have opted to receive the shots.
In the JAMA study, scientists at the Beth Israel Deaconess Medical Center in Boston and Harvard Medical School studied blood samples from 103 women who had received the Pfizer or Moderna vaccine between December 2020 and March 2021. Of these women, 30 had received the vaccine while pregnant, 16 while lactating and 57 while neither pregnant nor lactating.
The researchers analyzed the blood samples for signs that the shots had conferred some protection against the coronavirus. Immune responses are complex, and may involve both antibodies — proteins that can bind to and block the virus — and T cells, which help the body recognize the virus and destroy infected cells.
The vaccines produced similar responses in all three groups of women, eliciting both antibody and T-cell responses against the coronavirus, the scientists found. Of particular note, experts said, was the fact that the shots produced high levels of neutralizing antibodies, which can prevent the virus from entering cells, in both pregnant and nonpregnant women.
“Clearly, the vaccines were working in these people,” said Akiko Iwasaki, an immunologist at Yale University who was not involved in the research. “These levels are expected to be quite protective.”
The researchers also found neutralizing antibodies in the breast milk of vaccinated mothers and in umbilical cord blood collected from infants at delivery. “Vaccination of pregnant people and lactating people actually leads to transfer of some immunity to their newborns and lactating infants,” said Dr. Ai-ris Y. Collier, a physician-scientist at Beth Israel who is the first author of the paper.
The results are “really encouraging,” Dr. Iwasaki said. “There is this added benefit of conferring protective antibodies to the newborn and the fetus, which is all the more reason to get vaccinated.”
The scientists also measured the women’s immune responses to two variants of concern: B.1.1.7, which was first identified in Britain, and B.1.351, which was first identified in South Africa. All three groups of women produced antibody and T-cell responses to both variants after vaccination, although their antibody responses were weaker against the variants, especially B.1.351, than against the original strain of the virus, according to the study.
“These women developed immune responses to the variants, although the asterisk is that the antibody responses were reduced several-fold,” said Dr. Dan Barouch, a study author and virologist at Beth Israel. (Dr. Barouch and his colleagues developed the Johnson & Johnson vaccine, which was not included in this study.)
“Overall, it’s good news,” he added. “And it increases the data that suggests that there is a substantial benefit for pregnant women to be vaccinated.”
The researchers also found that 14 percent of pregnant women reported a fever after their second vaccine dose, compared to 52 percent of nonpregnant women. They did not observe any severe complications or side effects.
The study will continue, with researchers monitoring women’s longer-term immune responses. And larger epidemiological studies are still needed to confirm these lab-based results, Dr. Collier noted.
In the second study, a research team from Northwestern University and the Ann and Robert H. Lurie Children’s Hospital of Chicago examined the placentas from 200 women who gave birth between April 2020 and April 2021. Eighty-four of the women had received either the Pfizer or Moderna vaccine during pregnancy; the remainder had not received any coronavirus vaccine.
The placentas from vaccinated women were not any more likely to show signs of injury or abnormality than those from unvaccinated women, the researchers found.
“These data build upon the emerging data that’s come out about these vaccines and their safety in pregnant people,” Dr. Miller said. “These are translational data that suggests the placenta doesn’t see any injurious impact of the vaccine. And that’s really fantastic.”
The findings have limitations, she acknowledged. Because the vaccines were only authorized recently, most of the women in the study were vaccinated in the third trimester of pregnancy, and many of them were health care workers, who were among the first people eligible for the shots.
Dr. Miller and her colleagues are continuing to collect more data, including from patients who were vaccinated earlier in their pregnancies and who received the one-shot Johnson & Johnson vaccine.
“This is ongoing work,” Dr. Miller said. But they wanted to publish their preliminary data as soon as they had it, she added, “to help people make the best decision they can.”
Why Exercise Can Be So Draining for People With Rheumatoid Arthritis
Even a gentle session of leg lifts set off an exaggerated nervous system reaction in older women with rheumatoid arthritis.
Exercise can feel more difficult and draining than usual if you have rheumatoid arthritis, and it’s not just because of the stiff and painful joints caused by this autoimmune disorder. In a groundbreaking new experiment involving older women and exercise, researchers found that even a gentle session of leg lifts set off an exaggerated nervous system reaction in those with rheumatoid arthritis. Light exercise also negatively affected the inner workings of their muscles and blood vessels.
The findings build on earlier research about rheumatoid arthritis and the nervous system and raise pressing new questions about the best and safest ways for people with this disorder or similar autoimmune diseases to become and remain active.
Anyone who has rheumatoid arthritis or is close to someone who has it knows the havoc it creates in the body. Immune cells mistakenly attack healthy tissue, especially in joints, causing swelling, pain and deterioration, along with full-body inflammation and fatigue. Rheumatoid arthritis also often results in cardiovascular disease, which initially puzzled doctors, since the misguided immune cells do not directly target the heart or arteries.
But in recent years, researchers discovered that people with rheumatoid arthritis tend to have unusually twitchy sympathetic nervous systems. The sympathetic nervous system is the portion of our internal wiring that stimulates the fight-or-flight response, biochemically alerting our brains, heart, muscles and other bodily systems to brace ourselves for impending danger. The opposing parasympathetic nervous system, the Matthew McConaughey of our internal biology, lulls us, sending signals that quiet the sympathetic upsets.
But in rheumatoid arthritis patients, researchers found, the sympathetic system seems stuck in overdrive, keeping people’s internal operations constantly on edge. A result is a high risk for elevated blood pressure and heart rate, even when people are resting quietly, which contributes over time to cardiovascular disease.
Few of those earlier studies, though, looked at exercise, which also raises blood pressure and heart rates and changes nervous system reactions. Some past studies — and considerable anecdotal evidence — had indicated that people with rheumatoid arthritis feel more fatigue during and after activity than other exercisers. Their heart rates and blood pressures also remain stubbornly elevated for longer after workouts. But what might be going on inside their nerves and muscles leading to these reactions has been mostly unclear.
So, for the new study, which was published in February in The Journal of Physiology, scientists at the University of São Paulo in Brazil decided to ask people with rheumatoid arthritis to do a little resistance training. Turning to patients at the university’s rheumatology clinic, they recruited 33 older women with rheumatoid arthritis and another 10 older women without the condition, to serve as controls. Most of them, in both groups, were on various medications.
They invited all of their volunteers to the lab, drew blood, asked about their current pain levels, tested blood pressure and other health markers, and gently embedded tiny sensors beneath the skin in one leg to measure nervous system activity. Finally, they asked each woman to complete leg lifts with that leg, using a standard weight machine set to a low resistance. The women were supposed to lift repeatedly for three minutes — although some quit earlier than that — while the researchers tracked their blood pressures, nervous system reactions, and markers of muscular response, during and immediately afterward.
What they found when they compared results was that “the women with R.A. showed greater blood pressure and sympathetic responses” to the light workout than those in the control group, says Tiago Peçanha, a postdoctoral research associate at the University of São Paulo who was a co-author of the new study with his doctoral adviser Hamilton Roschel, the director of the university’s Laboratory of Assessment and Conditioning in Rheumatology, and others.
Their nerves seemed especially sensitive to the buildup of certain substances in the working muscles, the researchers concluded, which prompted the nerves to send urgent messages to nearby blood vessels, ordering them to contract. The result was lingering high blood pressure, during and after the workout.
These reactions were most marked among the rheumatoid arthritis patients with the highest levels of inflammatory activity in their blood before the exercise, the researchers found.
Taken as a whole, the findings indicate that physical activity can be extra difficult for people with rheumatoid arthritis, because their nervous systems may overreact to relatively minor changes inside the muscles.
But the findings do not suggest that those with the autoimmune disorder should avoid exercise, Dr. Roschel says. “Physical activity is highly recommended for people with R.A,” he points out. “But these individuals may require additional attention and support to engage in physical activity programs.”
If you have been diagnosed with rheumatoid arthritis, talk with your physician or an exercise physiologist about how best to exercise, he says. And if you begin a new routine, start slowly and perhaps keep a log of how you feel during workouts.
Of course, this study focused on older women with rheumatoid arthritis and a single session of very light resistance training. It is unknown whether the results apply equally to younger women or men with the condition, or whether other types of exercise, such as walking, may produce a similar response. It is also unknown how those with different autoimmune diseases or related conditions might be affected.
Dr. Roschel and his colleagues are looking into all of those questions, though. “We have also been conducting some exercise studies with patients who have recovered from Covid-19 in our lab, and they also present abnormal cardiorespiratory responses to exercise,” he says. They hope to publish additional studies soon.
Do I Have to Get the Covid Vaccine in My Arm?
Most people will roll up their sleeves for the injection, but some may want to consider an alternate body part.
By now most people are familiar with how the Covid-19 vaccine is typically administered: a quick jab to the upper arm. But there is a lesser known place on the body where the vaccine has also been approved for injection: the thigh.
While getting the vaccine in the thigh is rare, there are some groups of people who may want to consider it. If you fall into one of the categories below and think you would be better off getting the Covid-19 vaccine in your thigh instead of your arm, it’s best to discuss it first with your doctor.
Which adults might want to get a shot in the thigh?
People with a history or risk of lymphedema in both arms.
Lymphedema is a chronic and painful condition that causes swelling in parts of the body. It can develop in breast cancer patients, for example, who require surgery to remove lymph nodes from under the arm. Removal of the lymph nodes disrupts the flow of lymph, the extra fluid from tissues that would normally drain through the lymphatic system into the bloodstream, causing the fluid to back up and the breast, torso or arm to swell on the affected side.
In both the Moderna and Pfizer-BioNTech clinical vaccine trials, some participants experienced swollen lymph nodes at the armpit or the neck region two to four days following vaccination, on the same side where the shot was administered in the arm. This is a normal short-term side effect that means the body is responding to the vaccine. In the case of Moderna, the median duration of swelling was one to two days, and it lasted an average of 10 days in those receiving Pfizer-BioNTech.
For patients with lymphedema or at risk for lymphedema, however, this side effect could be concerning. If someone has lymphedema in both arms or if a patient is at risk of lymphedema in both arms, then some medical institutions are recommending that their patients get the Covid-19 vaccine in the thigh as a precautionary measure. The concern is that the vaccine could either make the arms swell even more or, for those who are at risk of lymphedema, create worrisome symptoms where there were none.
The immune response might also be less efficient if the shot is administered in an arm without lymph nodes or one that has impaired lymphatic drainage.
“The lymph vessels are responsible for draining fluid out of all of our tissues, so if your lymphatic drainage isn’t good, your tissues swell from fluid — and that would also mean you wouldn’t carry a vaccine very efficiently from tissue to lymph node,” said Marc Jenkins, director of the Center for Immunology at the University of Minnesota Medical School.
Patients who had lymph nodes removed from one arm may get the vaccine in the unaffected arm rather than the thigh, said Cheryl Brunelle, the associate director of the Lymphedema Research Program at Massachusetts General Hospital in Boston.
People who have (or had) breast cancer.
Swollen lymph nodes in the armpit can be a sign of breast cancer. If someone with a history of breast cancer didn’t know that the Pfizer-BioNTech or Moderna vaccines can produce swollen lymph nodes, it could be “very scary for her, thinking it may be a recurrence,” Ms. Brunelle said.
To alleviate potential concerns, people with a history of breast cancer can opt to get the vaccine in the thigh if they wish.
People who need a mammogram within six weeks of their Covid-19 vaccine.
Coronavirus vaccinations can cause enlarged lymph nodes in the armpit or near the collarbone that will show up as white blobs on mammograms and potentially be mistaken as a sign of cancer. The Society of Breast Imaging recommends trying to schedule your routine screening mammogram before your first Covid-19 vaccine dose or at least one month after your second vaccine dose. But an alternative plan would be to get the vaccine in your thigh instead.
“Injection in thigh would be extremely unlikely to lead to armpit nodes swelling,” Dr. Constance D. Lehman, the chief of breast imaging at Massachusetts General Hospital, told The New York Times earlier this month.
If you prefer to get the vaccine in your arm and have already scheduled your mammogram, you can keep that appointment — as well as your vaccine appointment — and call your breast imaging center ahead of time to let them know about the timing of your vaccine.
If you received the Covid vaccine in the arm in the last six weeks, your radiologist will expect to see lymph node swelling on the same side that you received the vaccine. This would be a normal finding unless the swelling continued for more than six weeks or there were other clinical concerns; in that case they would take more images as needed, Ms. Brunelle said.
Which vaccination sites offer thigh injections?
This could take a little persistence. Covid-19 vaccine sites primarily give people arm vaccinations: It’s quick, efficient and there’s no need to find a private room to disrobe. Because the vast majority of people will receive arm injections, some vaccination sites may not have staff who are trained to inject in the thigh.
“I just advise patients to call ahead, let the vaccine clinic know or the pharmacy know that they’re asking for the vaccine in the thigh,” Ms. Brunelle said. “I also counsel patients that if a local facility or practitioner giving the vaccine is not familiar with the thigh as an approved alternate site, the patient can share the C.D.C. Standing Orders document that lists the thigh as an alternative site for both the Pfizer and Moderna vaccines.”
In New York City, people visiting health department vaccination sites can speak with staff if they have concerns about getting the vaccine in the arm, said Michael Lanza, a health department spokesman. These sites also have “quiet rooms” where thigh injections can be performed discreetly, he added, but “it should only be done when medically necessary.”
What if I am a candidate for a thigh vaccine but I already had the vaccine injected in my arm?
Experts say not to worry if you already got vaccinated on the side where you had breast cancer or if you were vaccinated in the arm that had fewer lymph nodes; what is important is that you received the vaccine.
“We don’t want to scare women who already got vaccinated,” said Dr. Alphonse Taghian, director of the Lymphedema Research Program at Massachusetts General Hospital. “It is possible there will be no problem at all.”
To learn more, Dr. Taghian and Ms. Brunelle will be surveying current and former breast cancer patients about the side effects of the vaccine to better understand how many patients report swollen lymph nodes, as well as when and how long the symptom occurs. They hope to have results before the end of the year.
Dr. Taghian encourages patients with a history of cancer to contact their oncology team with questions or concerns, and to tell their doctor if they develop new signs of swelling.
Why are the vaccines typically injected in the arm?
The Covid-19 vaccines are designed to be injected into muscle, and the muscles of the upper arm are convenient for shots and thought to be less painful than some other areas of the body. But a vaccine can be injected into other muscles, provided they are near some of the hundreds of lymph nodes that exist in the body. The upper thigh, for example, is located near multiple lymph nodes and has already been shown to generate an effective immune response after vaccination.
Lymph nodes are “absolutely critical for generating immune responses,” said Dr. Akiko Iwasaki, a professor of immunobiology at Yale University.
When a vaccine enters the arm or thigh muscle, it gets carried into a nearby lymph node, she added. There, the vaccine is taken up by special cells that teach the white blood cells, known as T cells and B cells, to either become killer cells, which seek out and destroy coronavirus-infected cells, or antibody-secreting cells.
Decades ago, other vaccines were often injected into the buttocks. But scientists now understand that the layers of fat cells in our bottoms are too numerous to allow easy access to the muscles and lymph, making the immune response inefficient. In addition, vaccination in the buttocks is generally not done to avoid injury to the sciatic nerve.
¿Se puede tomar alcohol después de la vacuna para la covid?
Es poco probable que beber con moderación afecte la respuesta inmune a la vacuna, pero beber demasiado sí podría tener un impacto.
Tras un largo año y mucha expectación, vacunarse contra la COVID-19 puede ser motivo de celebración, lo que para algunos puede significar servirse una copa y brindar por su recién adquirida inmunidad. Pero, ¿puede el alcohol interferir en la respuesta inmunitaria?
La respuesta corta es que depende de la cantidad que bebas.
No hay pruebas de que tomar una o dos copas pueda reducir la eficacia de ninguna de las actuales vacunas para la covid que se administran en Estados Unidos (Pfizer, Moderna y Johnsoon & Johnson). Algunos estudios han descubierto incluso que, a largo plazo, el consumo de cantidades pequeñas o moderadas de alcohol podría beneficiar al sistema inmunitario al reducir la inflamación.
Por otro lado, los expertos afirman que el consumo excesivo de alcohol, especialmente a largo plazo, puede suprimir el sistema inmunitario e interferir potencialmente en la respuesta de la vacuna. Dado que el organismo puede tardar semanas en generar niveles protectores de anticuerpos contra el nuevo coronavirus después de la inyección para la covid, cualquier cosa que interfiera en la respuesta inmune sería motivo de preocupación
“Si realmente eres un bebedor moderado, no hay riesgo de tomar una copa en el momento de la vacuna”, dijo Ilhem Messaoudi, directora del Centro de Investigación de Virus de la Universidad de California, Irvine, quien ha realizado investigaciones sobre los efectos del alcohol en la respuesta inmune. “Pero hay que ser muy consciente de lo que significa realmente beber con moderación. Es peligroso beber grandes cantidades de alcohol porque los efectos en todos los sistemas biológicos, incluido el sistema inmunitario, son bastante graves y se producen con bastante rapidez una vez que se sale de esa zona moderada”.
El consumo moderado de alcohol se define generalmente como no más de dos bebidas al día para los hombres y un máximo de una bebida al día para las mujeres, mientras que el consumo excesivo se define como cuatro o más bebidas en cualquier día para los hombres y tres o más bebidas para las mujeres. Hay que tener en cuenta que una bebida “estándar” se considera 148 mililitros de vino, 44 mililitros de licores destilados o 355 mililitros de cerveza.
Algunas de las primeras preocupaciones sobre el alcohol y la vacuna para la covid comenzaron a circular después de que una funcionaria de salud rusa advirtió en diciembre que la gente debía evitar el alcohol durante dos semanas antes de vacunarse y abstenerse durante otros 42 días después. Según un informe de Reuters, la funcionaria afirmaba que el alcohol podía dificultar la capacidad del organismo para desarrollar inmunidad contra el nuevo coronavirus. Su advertencia provocó una fuerte reacción en Rusia, que tiene una de las tasas de consumo de alcohol más altas del mundo.
En Estados Unidos, algunos expertos afirman haber escuchado preocupaciones similares sobre si es seguro beber cerca del momento de la vacunación. “Hemos recibido muchas preguntas de nuestros pacientes sobre esto”, dijo Angela Hewlett, profesora asociada de enfermedades infecciosas que dirige el equipo para la enfermedad infecciosa covid en el Centro Médico de la Universidad de Nebraska. “Es comprensible que las personas que reciben estas vacunas quieran asegurarse de que están haciendo todo lo correcto para maximizar su respuesta inmunitaria”.
Los ensayos clínicos de las vacunas para la covid que actualmente están aprobadas para su uso por la Administración de Alimentos y Medicamentos (FDA por su sigla en inglés) no analizaron específicamente si el alcohol tenía algún impacto en la eficacia de las vacunas, dijo Hewlett. Es posible que haya más información al respecto en el futuro. Pero por ahora, la mayor parte de lo que se sabe proviene de investigaciones anteriores, incluidos los estudios que examinaron cómo el alcohol afecta al sistema inmunitario en los seres humanos y si dificulta la respuesta inmune en animales que recibieron otras vacunas.
Algo que queda claro a partir de los estudios es que el consumo excesivo de alcohol deteriora la respuesta inmune y aumenta la susceptibilidad a las infecciones bacterianas y víricas. Impide que las células inmunitarias se desplacen a los focos de infección y lleven a cabo sus funciones, como destruir los virus, las bacterias y las células infectadas; facilita que los agentes patógenos invadan sus células, y causa una serie de otros problemas.
En cambio, el consumo moderado de alcohol no parece tener este efecto. En un estudio, los científicos expusieron a 391 personas a cinco virus respiratorios diferentes y descubrieron que los bebedores moderados eran menos propensos a desarrollar resfriados, pero no si eran fumadores.
En otro estudio, Messaoudi y sus colegas proporcionaron a monos rhesus acceso a bebidas alcohólicas durante siete meses y luego observaron cómo respondía su organismo a una vacuna contra un poxvirus. Al igual que los humanos, algunos monos rhesus disfrutan del alcohol y beben mucho, mientras que otros muestran menos interés y se limitan a pequeñas cantidades. Los investigadores descubrieron que los animales que bebían mucho de forma crónica tenían una respuesta débil a la vacuna. “Tenían una respuesta inmune casi inexistente”, dijo Messaoudi.
Sin embargo, los animales que solo consumían cantidades moderadas de alcohol generaban la respuesta más fuerte a la vacuna, incluso en comparación con los abstemios que no consumían nada de alcohol. Los estudios realizados en ratas han encontrado un patrón similar: las que consumen grandes cantidades de alcohol solo tienen una débil respuesta inmune a las infecciones en comparación con los animales a los que se les da cantidades moderadas de alcohol o ninguna. Otros estudios han descubierto que cuando las personas beben moderadamente, parece que disminuyen los marcadores inflamatorios en la sangre.
Otra razón para moderar el consumo de alcohol es que beber en exceso —junto con la resaca que puede provocar— puede amplificar los efectos secundarios que pueda tener la vacuna para la covid, como fiebre, malestar o dolores corporales, y hacer que te sientas peor, dijo Hewlett, del Centro Médico de la Universidad de Nebraska. Hewlett decidió no beber después ser vacunada contra la covid. Pero dijo que la gente debería sentirse libre de beber siempre que lo haga dentro de lo razonable.
“Tomar una copa de champán probablemente no inhibirá ninguna respuesta inmune”, dijo. “Creo que tomar una bebida de celebración con moderación está bien”.
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Anahad O’Connor cubre temas de salud, ciencia, nutrición y otros. También es el autor de libros de salud exitosos como Never Shower in a Thunderstorm y The 10 Things You Need to Eat.
Can You Have Alcohol After the Covid Vaccine?
Moderate drinking is unlikely to impair the immune response to the Covid vaccine, but heavy drinking might.
After a long year and a lot of anticipation, getting the Covid-19 vaccine can be cause for celebration, which for some might mean pouring a drink and toasting to their new immunity. But can alcohol interfere with your immune response?
The short answer is that it depends on how much you drink.
There is no evidence that having a drink or two can render any of the current Covid vaccines less effective. Some studies have even found that over the longer term, small or moderate amounts of alcohol might actually benefit the immune system by reducing inflammation.
Heavy alcohol consumption, on the other hand, particularly over the long term, can suppress the immune system and potentially interfere with your vaccine response, experts say. Since it can take weeks after a Covid shot for the body to generate protective levels of antibodies against the novel coronavirus, anything that interferes with the immune response would be cause for concern.
“If you are truly a moderate drinker, then there’s no risk of having a drink around the time of your vaccine,” said Ilhem Messaoudi, director of the Center for Virus Research at the University of California, Irvine, who has conducted research on the effects of alcohol on the immune response. “But be very cognizant of what moderate drinking really means. It’s dangerous to drink large amounts of alcohol because the effects on all biological systems, including the immune system, are pretty severe and they occur pretty quickly after you get out of that moderate zone.”
Moderate drinking is generally defined as no more than two drinks a day for men and a maximum of one drink a day for women, whereas heavy drinking is defined as four or more drinks on any day for men and three or more drinks for women. Keep in mind that one “standard” drink is considered five ounces of wine, 1.5 ounces of distilled spirits, or 12 ounces of beer.
Some of the first concerns about alcohol and Covid vaccination began circulating after a Russian health official who warned in December that people should avoid alcohol for two weeks before getting vaccinated and then abstain for another 42 days afterward. According to a Reuters report, the official claimed that alcohol could hamper the body’s ability to develop immunity against the novel coronavirus. Her warning sparked a fierce backlash in Russia, which has one of the world’s highest drinking rates.
In the United States, some experts say they have heard similar concerns about whether it is safe to drink around the time of vaccination. “We’ve been getting a lot of questions from our patients about this,” said Dr. Angela Hewlett, an associate professor of infectious diseases who directs the Covid infectious diseases team at the University of Nebraska Medical Center. “Understandably, people who are receiving these vaccines want to make sure they’re doing all the right things to maximize their immune response.”
Clinical trials of the Covid vaccines that are currently approved for use by the Food and Drug Administration did not specifically look at whether alcohol had any impact on the effectiveness of the vaccines, Dr. Hewlett said. It’s possible that there will be more information on that in the future. But for now, most of what is known comes from previous research, including studies that examined how alcohol affects the immune system in humans and whether it hinders the immune response in animals that received other vaccines.
One thing that is clear from studies is that heavy alcohol consumption impairs the immune response and increases your susceptibility to bacterial and viral infections. It prevents immune cells from traveling to sites of infection and carrying out their duties, like destroying viruses, bacteria and infected cells; makes it easier for pathogens to invade your cells, and causes a host of other problems.
In contrast, moderate drinking does not seem to have this effect. In one study, scientists exposed 391 people to five different respiratory viruses and found that moderate drinkers were less likely to develop colds, but not if they were smokers.
In another study, Dr. Messaoudi and colleagues provided rhesus monkeys access to alcoholic beverages for seven months and then looked at how their bodies responded to a vaccine against poxvirus. Much like humans, some rhesus monkeys enjoy alcohol and will drink a lot, while others show less interest and will limit themselves to small amounts. The researchers found that the animals that were chronically heavy drinkers had a weak response to the vaccine. “They had almost a nonexistent immune response,” Dr. Messaoudi said.
The animals that consumed only moderate amounts of alcohol, however, generated the strongest response to the vaccine, even compared to the teetotalers that consumed no alcohol at all. Studies in rats have found a similar pattern: Those consuming large amounts of alcohol have only a weak immune response to infections compared to animals given moderate amounts of alcohol or none at all. Other studies have found that when people drink moderately, it seems to lower inflammatory markers in their blood.
Another reason to moderate your alcohol intake is that heavy drinking — along with the hangover that can ensue — can potentially amplify any side effects you might have from the Covid vaccine, including fever, malaise or body aches, and make you feel worse, said Dr. Hewlett of the University of Nebraska Medical Center. Dr. Hewlett chose not to drink after getting the Covid vaccine. But she said that people should feel free to imbibe so long as they drink within reason.
“Having a glass of champagne probably won’t inhibit any immune response,” she said. “I think having a celebratory beverage in moderation is fine.”
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Vaccines Are Effective Against the New York Variant, Studies Find
The research adds to a growing number of findings suggesting the Pfizer and Moderna shots are protective against the variants identified so far.
For weeks, New Yorkers have witnessed the alarming rise of a homegrown variant of the coronavirus that has kept the number of cases in the city stubbornly high. City officials have repeatedly warned that the variant may be more contagious and may dodge the immune response.
On that second point, at least, they can now breathe easier: Both the Pfizer-BioNTech and Moderna vaccines will effectively prevent serious illness and death from the variant, two independent studies suggest.
Antibodies stimulated by those vaccines are only slightly less potent at controlling the variant than the original form of the virus, both studies found.
“We’re not seeing big differences,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York and a member of the team that published one of the studies on Thursday.
The bottom line? “Get vaccinated,” he said.
The results are based on laboratory experiments with blood samples from small numbers of vaccinated people and have not yet been peer-reviewed. Still, they are consistent with what is known about similar variants, several experts said, and they add to a growing body of research that suggests that the two main vaccines in the United States are protective against all of the variants identified so far.
“The take-home message is that the vaccines are going to work against the New York variant and the South African variant and the U.K. variant,” said Nathan Landau, a virologist at N.Y.U.’s Grossman School of Medicine who led the study.
The vaccines spur the body to mount an expansive immune response, with thousands of types of antibodies and several types of immune cells. One subset of these immune fighters, called neutralizing antibodies, is essential for preventing infection. But even when neutralizing antibodies are in short supply or even absent, the rest of the immune system may marshal enough of a defense to fend off serious illness and death.
In both new studies, neutralizing antibodies from vaccinated people were better at thwarting the virus than those from people who developed antibodies from being sick with Covid-19. Direct comparison of the two sets of antibodies offered a possible explanation: Antibodies from vaccinated people are distributed across a broader range of parts of the virus, so no single mutation has a big impact on their effectiveness — making vaccines a better bet against variants than immunity from natural infection.
The variant first identified in New York, known to scientists as B.1.526, raced through the city after its initial discovery in November. It accounted for one in four diagnosed cases by November and nearly half of cases as of April 13. The variant that brought Britain to a standstill, B.1.1.7, is also circulating widely in New York. Together, the two add up to more than 70 percent of coronavirus cases in the city.
The worry about the variant identified in New York has centered on one form of it, which contains a mutation that scientists are calling Eek. The Eek mutation subtly alters the shape of the virus, making it difficult for antibodies to target the virus and, as a result, undercutting the vaccines.
In the second study, Dr. Landau’s team found that the Pfizer and Moderna vaccines are only marginally less protective against the variant that devastated Britain and against forms of the variant discovered in New York that don’t contain the Eek mutation.
Several laboratory studies have shown that antibodies induced by the Pfizer and Moderna vaccines are slightly less powerful against a third variant, one identified in South Africa, which also contains Eek. Other vaccines fared worse. South Africa suspended use of the AstraZeneca vaccine after clinical trials showed that the vaccine did not prevent mild or moderate illness from the variant that was circulating there.
“It already started out as a lower level in terms of the immunity that it generated,” Dr. Nussenzweig said of the AstraZeneca vaccine. Referring to the Pfizer and Moderna shots, he said, “We’re so lucky in this country to have these vaccines compared to the rest of the world.”
Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai who was not involved in either of the new studies, said he was more concerned about other countries’ vaccine programs than about the variants themselves.
“I am less concerned about variants than I was two months ago,” he said, but added: “I’m worried about countries that don’t have enough vaccine and that don’t have that vaccine rollout. I’m not worried anymore about the U.S., honestly.”
Dr. Landau’s team also tested monoclonal antibodies used to treat Covid-19 against the variants. They found that the cocktail of monoclonal antibodies made by Regeneron worked as well against the variant discovered in New York as against the original virus.
The studies are reassuring, but they indicate that the Eek mutation is one to watch, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.
“This could certainly be a step toward the virus becoming somewhat more resistant to infection- and vaccine-mediated immunity,” Dr. Bloom said. “I don’t think it’s something that people need to immediately become alarmed about, but it definitely impresses us as important.”
Dr. Bloom led the analysis comparing vaccine-induced antibodies with those produced by natural infection. He found that the most powerful antibodies bind to multiple sites in a key part of the virus. Even if a mutation affects the binding in one site in this region, antibodies that target the remaining sites would still be protective.
Antibodies induced by the vaccine cover many more sites across this region than those from natural infection — and so are less likely to be affected by a mutation in any one site.
The study looked only at antibodies stimulated by the Moderna vaccine, but the results are likely to be the same for the Pfizer-BioNTech vaccine, he added.
“This could potentially be a good thing as the virus is creating mutations,” Dr. Bloom said.
Researchers Are Hatching a Low-Cost Coronavirus Vaccine
A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.
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.
First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.
“It’s a home run for protection,” said Dr. Bruce Innes of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NVD-HXP-S. “I think it’s a world-class vaccine.”
2P to the rescue
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.
In the case of the coronavirus, the best target for the immune system is the protein that covers its surface like a crown. The protein, known as 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.
This insight emerged long before the Covid-19 pandemic. In 2015, another coronavirus appeared, causing a deadly form of pneumonia called MERS. Jason McLellan, a structural biologist then at the Geisel School of Medicine at Dartmouth, and his colleagues set out to make a vaccine against it.
They wanted to use the spike protein as a target. But they had to reckon with the fact that the spike protein is a shape-shifter. As the protein prepares to fuse to a cell, it contorts from a tulip-like shape into something more akin to a javelin.
Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.
Dr. McLellan and his colleagues used standard techniques to make a MERS vaccine but ended up with a lot of postfusion spikes, useless for their purposes. Then they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.
The resulting spike — called 2P, for the two new proline molecules it contained — was far more likely to assume the desired tulip shape. 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.
Two prolines are good; six are better
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.
“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.
In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.
The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike 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.
With a little help from eggs
The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.
The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.
The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.
In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.
For years, scientists had been 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.
PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.
“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”
The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.
“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.
PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals 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.’”
Researchers Are Hatching a Low-Cost Covid-19 Vaccine
A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.
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.
First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.
“It’s a home run for protection,” said Dr. Bruce Innes of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NVD-HXP-S. “I think it’s a world-class vaccine.”
2P to the rescue
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.
In the case of the coronavirus, the best target for the immune system is the protein that covers its surface like a crown. The protein, known as 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.
This insight emerged long before the Covid-19 pandemic. In 2015, another coronavirus appeared, causing a deadly form of pneumonia called MERS. Jason McLellan, a structural biologist then at the Geisel School of Medicine at Dartmouth, and his colleagues set out to make a vaccine against it.
They wanted to use the spike protein as a target. But they had to reckon with the fact that the spike protein is a shape-shifter. As the protein prepares to fuse to a cell, it contorts from a tulip-like shape into something more akin to a javelin.
Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.
Dr. McLellan and his colleagues used standard techniques to make a MERS vaccine but ended up with a lot of postfusion spikes, useless for their purposes. Then they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.
The resulting spike — called 2P, for the two new proline molecules it contained — was far more likely to assume the desired tulip shape. 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.
Two prolines are good; six are better
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.
“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.
In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.
The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike 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.
With a little help from eggs
The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.
The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.
The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.
In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.
For years, scientists had been 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.
PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.
“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”
The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.
“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.
PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals 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.’”