Lab-grown ‘mini brains’ hint at potential treatment options for motor neurone disease and frontotemporal dementia

Cambridge researchers have developed ‘mini brains’ that allow them to study a fatal and untreatable neurological disorder causing paralysis and dementia — and for the first time have been able to grow these for almost a year.
A common form of motor neurone disease, amyotrophic lateral sclerosis, often overlaps with frontotemporal dementia (ALS/FTD) and can affect younger people occurring mostly after the age of 40-45. These conditions cause devastating symptoms of muscle weakness with changes in memory, behaviour and personality. Being able to grow small organ-like models (organoids) of the brain allows the researchers to understand what happens at the earliest stages of ALS/FTD, long before symptoms begin to emerge, and to screen for potential drugs.
In general, organoids, often referred to as ‘mini organs’, are being used increasingly to model human biology and disease. At the University of Cambridge alone, researchers use them to repair damaged livers, study SARS-CoV-2 infection of the lungs and model the early stages of pregnancy, among many other areas of research.
Typically, researchers take cells from a patient’s skin and reprogramme the cells back to their stem cell stage — a very early stage of development at which they have the potential to develop into most types of cell. These can then be grown in culture as 3D clusters that mimic particular elements of an organ. As many diseases are caused in part by defects in our DNA, this technique allows researchers to see how cellular changes — often associated with these genetic mutations — lead to disease.
Scientists at the John van Geest Centre for Brain Repair, University of Cambridge, used stem cells derived from patients suffering from ALS/FTD to grow brain organoids. These resemble parts of the human cerebral cortex in terms of their embryonic and fetal developmental milestones, 3D architecture, cell-type diversity and cell-cell interactions.
Although this is not the first time scientists have grown mini brains from patients with neurodegenerative diseases, most efforts have only been able to grow them for a relatively short time frame, representing a limited spectrum of dementia-related disorders. In findings published today in Nature Neuroscience, the Cambridge team reports growing these models for 240 days from stem cells harbouring the commonest genetic mutation in ALS/FTD, which was not previously possible — and in unpublished work the team has grown them for 340 days.

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Fingerprinting proteins with force

As scientists have probed the mysteries of life down to smaller and smaller scales, they have invented tools to help them understand what they observe. Determining the identity of DNA and RNA molecules has now become commonplace thanks to the commercial development of next-generation sequencing technologies, but the same is not yet true of proteins, which are critically important players in nearly all biological processes. Proteins are much more complex than DNA and RNA, and are often chemically modified, making the goal of easily identifying single proteins within a sample (single-molecule proteomics) challenging to achieve.
Now, scientists working at the Molecular Robotics Initiative within the Wyss Institute at Harvard University, the Blavatnik Institute at Harvard Medical School (HMS), and Boston Children’s Hospital (BCH) have used DNA, the fundamental stuff of life itself, to create what may be the world’s tiniest ruler for measuring proteins.
Dubbed “DNA Nanoswitch Calipers” (DNC), this technology enables researchers to perform distance measurements on single peptides (the building blocks of proteins) with high precision by applying small amounts of force. By rapidly making many distance measurements on the same molecule, DNC creates a unique “fingerprint” that can be used to identify it in subsequent experiments. The achievement is reported in Nature Nanotechnology.
“When you’re trying to understand something in biology, there are two main methods of inquiry: you can observe your subject in its natural state, or you can perturb it and see how it reacts. Observations can provide lots of great biological information, but sometimes the best way to learn about something is to physically interact with it,” said co-corresponding author Wesley Wong, Ph.D., an Associate Faculty Member at the Wyss Institute and Associate Professor at HMS who is also an Investigator at BCH. “Determining the pattern of amino acids within a peptide molecule by applying force is a new paradigm in the ongoing scientific quest for techniques that will enable us to sequence proteins as easily as we currently sequence DNA.”
Use the force
DNC is based on the underlying technology of the DNA nanoswitch: a single strand of DNA with molecular “handles” attached to it at multiple points along its length. When two of these handles bind to each other, they create a loop in the DNA strand, and the overall length of the strand is shortened. When force is applied to pull the handles apart, the strand extends back to its original length. The difference between the length of the strand in its looped and unlooped states reflects the size of the loop, and thus the distance between the handles.

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Targeted drug shows activity against brain metastases in kidney cancer

A targeted drug has shown promising activity against brain metastases resulting from kidney cancer, achieving a 50 percent response rate, and supporting further studies of the drug in this patient group whose poor prognosis has created a significant unmet need.
The drug, cabozantinib, is a tyrosine kinase inhibitor that attacks several targets in cancer cells. It has been approved to treat advanced renal cell (kidney) cancer, but it has undergone very little testing in patients with brain metastases. Historically these patients are typically excluded from clinical trials out of concern for poor life expectancy and intervention tolerability. The new report in JAMA Oncology suggests that cabozantinib can potentially pass through the blood-brain barrier to reach the metastases, some of which shrank significantly, said senior author Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute.
The drug was tolerated in two cohorts of patients, amounting to 88 individuals with brain metastases from kidney cancer. Some patients also received local treatment with surgery or radiation, while others did not. Patients in one cohort survived for a median of 15 months, and 16 months in the other cohort.
Choueiri said that kidney cancer spreads to the brain in 2-10% of patients, causing significant morbidity and mortality, and the metastases are usually treated with surgery and/or radiation. Until now, systemic treatment with targeted drugs like sunitinib has proven relatively ineffective, and immunotherapy drugs have not shown much benefit either. “A lot of drugs that work well outside the brain don’t work well for brain metastases,” Choueiri noted.
A few isolated case reports of cabozantinib in kidney cancer patients with brain metastases suggested potential benefit, prompting the new trial. “Given the sparse literature and high clinical need, we sought to assess the activity and safety of cabozantinib in patients with brain metastases from renal cell cancer, leveraging an international multicenter collaboration,” the researchers explained.
Following treatment with cabozantinib, “we measured the dimension of the metastases in the brain and saw a response rate that was higher than what we usually expect, and there were some nice examples of metastases really shrinking,” said Choueiri. However, he cautioned, some of the responses were not durable and the tumors became resistant after several months.
The study was retrospective. Choueiri said a prospective phase II trial of cabozantinib is under way in France, “and hopefully this will be definitive.”
While surgery and radiation currently are the gold standard for treating brain metastases in kidney cancer, Choueiri said these modalities don’t always work or can’t be used in certain locations in the brain. “It would be good to have a systemic option for these patients,” he said.
Most kidney cancer patients with brain metastases also have metastatic spread to other organs. The new study showed that the response rate with cabozantinib treatment was roughly the same for these extracranial metastases as it was for the brain metastases.
The first two authors of the report are Laure Hirsch, MD, MsC, and Nieves Martinez Chanza, MD, PhD, both formerly of Dana-Farber and now at Cochin Hospital, University of Paris, France and the Jules Bordet Cancer Institute, Brussels, Belgium, respectively.
Choueiri reports personal fees from Merck, Bristol Myers Squibb, Roche, EMDSerono, AstraZeneca, Exelixis, Pfizer, and Eli Lilly during the conduct of the study; personal fees from the National Comprehensive Cancer Network, the Genitourinary Cancers Steering Committee of the National Cancer Institute, continuing medical education programs related to genitourinary oncology, and various national and international committees and programs outside of the submitted work; and support from the Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence (2P50CA101942-16) and program (5P30CA006516-56), the Kohlberg Chair at Harvard Medical School, the Michael Brigham Fund, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber.

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Parents, Will You Vaccinate Your Children for Covid?

Tell us whether you plan to have your children immunized and what factors led to your decision.A child receives a second dose of the Pfizer coronavirus vaccine during a clinical trial earlier this year.Shawn Rocco/Duke Health/Via ReutersWith the Food and Drug Administration likely to authorize a Covid vaccine for children ages 5 to 11, the Biden administration announced that it would distribute millions of doses for young patients. But recent surveys show that many parents are wrestling with whether to allow the shots for their children.If you have children who will be eligible, Times journalists would like to know your thoughts. Your name and comments may be published, but your contact information will not. A reporter or editor from The Times may follow up with you directly.Will you permit your children ages 5 to 11 to have a Covid vaccine?

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Pfizer says new data show booster shots of its vaccine are highly protective against Covid.

Booster shots in adults who received the Pfizer-BioNTech vaccine were highly effective at preventing symptomatic Covid-19 breakthrough infections, Pfizer announced on Thursday.The company said that out of more than 5,000 Pfizer-BioNTech vaccine recipients enrolled in its study who received a booster shot, only five later developed symptomatic disease, compared with 109 people among a similar group that received a placebo instead of a booster dose.The news arrived as an advisory committee to the Centers for the Disease Control and Prevention debates whether Americans should receive booster shots of the Moderna and Johnson & Johnson vaccines.The company claimed the findings came from the first randomized efficacy trial of booster shots. But the results, announced in a news release, have not been peer-reviewed or published in a medical journal.Last month, the Food and Drug Administration authorized Pfizer-BioNTech booster shots for people 65 and over, people who are at high risk of severe Covid-19, and those who are at elevated risk of exposure because of where they work or live. That decision was based on limited effectiveness data.The new findings appear to bolster proof that booster shots are highly effective, though the trial participants were only followed for a median period of two and a half months after receiving the booster.“These important data add to the body of evidence suggesting that a booster dose of our vaccine can help protect a broad population of people from this virus and its variants,” said Dr. Ugur Sahin, founder and chief executive of BioNTech.The results will be shared with the F.D.A. and its European equivalent, the European Medicines Agency, as well as other international regulatory agencies, according to Albert Bourla, Pfizer’s chief executive.The randomized controlled trial of the booster included more than 10,000 participants aged 16 and older, half of whom received a booster that contains the same amount of vaccine as each of the two primary doses, and half of whom received a placebo.The booster was given an average of 11 months after the initial regimen, and participants were monitored for symptoms of Covid that developed between a week and 2.5 months after the booster, on average.Stratified analyses showed the relative efficacy rate of 95.6 percent for the boosters was consistent regardless of age, sex, race, ethnicity or chronic medical conditions.Slightly more than half of the participants were between 16 and 55 years old, and just under one quarter were 65 or older. The companies said that they had not identified any new side effects or safety concerns during the trial.

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What Are Next Steps as C.D.C. Panel Considers Moderna and J. & J. Boosters?

An independent committee of experts to the Centers for Disease Control and Prevention is meeting on Thursday for discussion on booster shots for people who have received the Moderna and Johnson & Johnson coronavirus vaccines.The panel will also consider a strategy known as “mix and match,” allowing for people to receive a booster of a different Covid-19 vaccine than the one they initially received.On Wednesday, the Food and Drug Administration authorized all three approaches, signing off on boosters for many Americans who got the Moderna or Johnson & Johnson vaccines, just as it did last month for Pfizer-BioNTech recipients. The F.D.A. also gave its blessing to allowing people eligible for boosters to get the extra dose of a different brand from they one they originally received.But that decision was not the end of the regulatory road. The C.D.C. and individual states still have roles to play. In practice, who will get the shots and when depends to a great degree on the C.D.C.’s final guidance. The agency’s recommendations do not bind state and local officials, but they hold great sway in the medical community and serve as a blueprint for policymakers across the country.Here are the next steps:The C.D.C.The panel meeting on Thursday is the Advisory Committee on Immunization Practices. It is made up of independent experts that advise the agency on scientific questions, and even though its recommendations are not final, the agency often follows them.After the panel makes it recommendations, the C.D.C.’s director, Dr. Rochelle P. Walensky, will issue guidance that will influence the actions of states, hospitals, pharmacies and other entities that distribute the vaccines.Last month, Dr. Walensky broke from the panel’s advice when she decided that frontline workers should receive booster shots of the Pfizer-BioNTech vaccine. Such instances are rare, however.The statesOnce the C.D.C. issues its guidance, the baton is passed to state health authorities. Health agencies in the states usually follow the C.D.C.’s advice and real-world action can be swift. After the agency ruled on the Pfizer boosters, the shots began to be administered that day.

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Back pain common among astronauts offers treatment insights for the earth-bound

With growing numbers of humans venturing into space, experts predict an increase in the number of people experiencing the physical toll of such travel, including highly common forms of back pain.
The prediction comes in a new report by researchers at Johns Hopkins Medicine, published in the September issue of Anesthesiology, based on a comprehensive review of past studies measuring the effects of space travel on the spine, and exploring methods to prevent, diagnose, and treat back pain. The scientists say further study among astronauts of these methods — including specialized suits and certain exercises — may provide insights for treating back pain in the estimated 80% of Earth-bound people who experience some form of it over their lifetimes.
Steven Cohen, M.D., professor of anesthesiology and critical care medicine at Johns Hopkins and a retired Army colonel. “Perhaps more importantly, insight into back pain in space travelers may provide usable information to treat back pain in other populations.”
An Aching Back: A Common Low Gravity-Related Pain
According to the review, past studies of astronauts have shown that 52% of space travelers report some form of back pain in the first two to five days of space travel. That figure is based on a retrospective study of 722 space flights worldwide published in Aerospace Medicine and Human Performance in 2012. The condition is now dubbed “space adaptation back pain,” and although 86% of cases were mild, the pain was enough to hinder an astronaut’s ability to complete tasks.
In addition to the studies among astronauts, a study from the University of Innsbruck in Austria showed that nearly half of military helicopter pilots and crewmembers who experience fluctuating gravitational forces report low back pain. The pilots are almost three times more likely to develop lumbar (lower back) disc herniation — an injury to the soft connective cushioning in the spine — compared with the general population. Astronauts are more than four times as likely to herniate a disc, according to a NASA study in 2010, and the risk was even higher in the first year after returning to Earth.

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Research breakthrough could mean better treatment for patients with most deadly form of brain tumor

Scientists studying the most common and aggressive type of brain tumour in adults have discovered a new way of analysing diseased and healthy cells from the same patient.
Crucially, the work which has been funded by the charity Brain Tumour Research could pave the way for truly personalised treatment for patients diagnosed with glioblastoma multiforme (GBM). Only 25% of patients with this type of brain tumour survive for more than one year and just 5% live for more than five years.
A team at the Brain Tumour Research Centre of Excellence at Queen Mary University of London has established an entirely new experimental research pipeline which, in a trial involving ten patients, has revealed new insights into how GBM develops, identifying potential new targets for individualised treatments. It could also help predict a patient’s response to drugs currently in clinical use for other diseases which would be extremely valuable as the average survival time for this type of brain tumour is just 12 to 18 months.
Their paper, Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells (SYNGN) in glioblastoma, is published in the high impact journal Nature Communications today (Thursday 21 October). Professor Silvia Marino, who leads the team, said: “We have used this powerful technique to identify changes in the function of genes that occur in GBM that do not entail a change in the genetic code (epigenetics). This has revealed new insights for how GBM develops and identified potential new targets for individualised treatments.”
By using a combination of laboratory work and sophisticated analytical computer programmes, the team at Queen Mary has identified significant molecular differences which could be exploited to develop new treatments. It is an innovative approach enabling the comparison of normal and malignant cells from the same patient helping to identify genes that play a role in growth of the tumour.
The research is particularly significant as GBM is the most common malignant brain tumour in adults. Its aggressive nature means it spreads extensively into surrounding brain tissue making complete removal by surgery almost impossible. It is extremely resistant to radiotherapy and chemotherapy meaning it is very likely to recur following treatment.
Hugh Adams, spokesman for Brain Tumour Research, said: “The complex nature of this particular tumour type means that the standard of care for these patients has not changed in a generation so this research brings much-needed hope for the future. One of the main challenges in developing effective treatments for GBM is that the tumour exhibits significant variation between patients and there can even be significant variation within a single patient’s tumour. These variations can arise from change to the cell’s genetic code — known as mutations — combined with changes to how specific genes are controlled.
“There is strong evidence that GBM cells develop from neural stem cells but previous studies have not been able to compare tumour cells and their putative cell of origin from the same person. Prof Marino and her team have now harnessed state-of-the-art stem cell technologies and next-generation DNA sequencing methods to compare diseased and healthy cells from the same patient. Their results have shown how this approach can reveal novel molecular events that appear to go awry when GBM develops, thereby identifying targets for potentially new treatments.”
The results of the team’s work have shown how this approach can reveal novel molecular targets for potentially new treatments. For example, the results reveal how some GBM tumours can control the movement of regulatory T cells, a type of immune cell and has also revealed epigenetic changes that could be used to predict the response to drugs currently in clinical use.
Brain tumours kill more children and adults under the age of 40 than any other cancer yet historically just 1% of the national spend on cancer research has been allocated to this devastating disease.
Brain Tumour Research funds sustainable research at dedicated centres in the UK. It also campaigns for the Government and the larger cancer charities to invest more in research into brain tumours in order to speed up new treatments for patients and, ultimately, to find a cure. The charity is calling for a national annual spend of £35 million in order to improve survival rates and patient outcomes in line with other cancers such as breast cancer and leukaemia and is also campaigning for greater repurposing of drugs.
Story Source:
Materials provided by Queen Mary University of London. Note: Content may be edited for style and length.

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US surgeons test pig kidney transplant in a human

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesUS surgeons say they have successfully given a pig’s kidney to a person in a transplant breakthrough they hope could ultimately solve donor organ shortages. The recipient was brain-dead, meaning they were already on artificial life support with no prospect of recovering. The kidney came from a pig that had been genetically modified to stop the organ being recognised by the body as “foreign” and being rejected. The work has not yet been peer-reviewed or published. Experts say it is the most advanced experiment in the field so far. Similar tests have been done in non-human primates, but not people, until now. Using pigs for transplants is not a new idea though. Pig heart valves are already widely used in humans.And their organs are a good match for people when it comes to size. During the operation at the New York University Langone Health medical centre, the surgeons connected the donor pig kidney to the blood vessels of the brain-dead recipient to see if it would function normally once plumbed in, or be rejected. Image source, NYU LangoneOver the next two-and-a-half days they closely monitored the kidney, running numerous checks and tests. Lead investigator Dr Robert Montgomery told the BBC’s World Tonight programme: “We observed a kidney that basically functioned like a human kidney transplant, that appeared to be compatible in as much as it did all the things that a normal human kidney would do.”It functioned normally, and did not appear to be undergoing rejection.”A transplant recipient himself, Dr Montgomery says there is an urgent need for finding more organs for people on waiting lists, although he acknowledges his work is controversial.”I certainly understand the concern and what I would say is that currently about 40% of patients who are waiting for a transplant die before they receive one. “We use pigs as a source of food, we use pigs for medicinal uses – for valves, for medication. I think it’s not that different.”He said it was still early research and more studies were needed, but added: “It gives us, I think, new confidence that it’s going to be all right to move this into the clinic.”Image source, NYU LangoneDr Maryam Khosravi, a kidney and intensive care doctor who works for the NHS in the UK, said: “Animal to human transplantation has been something that we have studied for decades now, and it’s really interesting to see this group take that step forward.”On the ethics, she said: “Just because we can doesn’t mean we should. I think the community at large needs to answer these questions.”A spokesperson for NHS Blood and Transplant, said matching more human donors remained the priority for now: “There is still some way to go before transplants of this kind become an everyday reality.”While researchers and clinicians continue to do our best to improve the chances for transplant patients, we still need everyone to make their organ donation decision and let their family know what they want to happen if organ donation becomes a possibility.” NYU Langone HealthThe BBC is not responsible for the content of external sites.

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C.D.C. Panel to Debate Boosters and 'Mix-and-Match' Strategy

As the latest wave of the virus ebbs in most parts of the United States, advisers to the Centers for Disease Control and Prevention will meet on Thursday to evaluate which Americans need extra doses of the coronavirus vaccines made by Moderna and Johnson & Johnson.They will also discuss the so-called mix-and-match strategy — whether people fully immunized with one company’s vaccine should be allowed to switch to a different one for their booster shot.On Wednesday, the Food and Drug Administration authorized booster shots for millions of people who received the Moderna and Johnson & Johnson vaccines, just as it did for recipients of Pfizer-BioNTech shots last month. The F.D.A. also gave the green light for people eligible for boosters to get an extra dose of a different brand from the one they first received.But in practice who will get the shots and when depends greatly on the C.D.C.’s final guidance. Though the agency’s recommendations do not bind state and local officials, they hold great sway in the medical community.Regardless of the tenor of the discussion, the final recommendations from the C.D.C.’s panel — the Advisory Committee on Immunization Practices — are unlikely to hold surprises. The committee is expected to endorse additional doses of the vaccines for many Americans and to strive to bring the country closer to fulfilling President Biden’s promise to provide boosters to all adults.It will not happen without some misgivings, however.Some of the C.D.C.’s advisers last month voiced strong reservations about a booster of the Pfizer-BioNTech vaccine, saying the science did not support additional shots for anyone other than adults over 65. A majority voted to recommend booster shots for people with certain medical conditions that increase the risk of Covid-19.The committee did not support boosters for people whose jobs expose them to the virus — but in a highly unusual move, Dr. Rochelle P. Walensky, the C.D.C.’s director, overturned their decision.“It is going to be a difficult meeting, because I suspect that the science won’t have changed much,” said Dr. Sarah S. Long, a pediatrician and infectious diseases expert at Drexel University in Philadelphia. “I can see making it clear that we still don’t think this is the right approach, and Dr. Walensky would have to override it.”A similar dynamic played out on the expert panel advising the F.D.A. at a meeting last week. Several advisers to the F.D.A. criticized the paucity of evidence supporting a Johnson & Johnson booster and expressed discomfort at having to decide on the booster before the F.D.A. had carefully vetted the data.Still, they unanimously voted in favor of a second Johnson & Johnson shot for adults who had received that vaccine because it was clear that two doses would be more protective than one, according to one member of the panel, Dr. Paul A. Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia..css-1kpebx{margin:0 auto;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1kpebx{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-1kpebx{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-1kpebx{font-size:1.25rem;line-height:1.4375rem;}}.css-1gtxqqv{margin-bottom:0;}.css-k59gj9{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;width:100%;}.css-1e2usoh{font-family:inherit;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;border-top:1px solid #ccc;padding:10px 0px 10px 0px;background-color:#fff;}.css-1jz6h6z{font-family:inherit;font-weight:bold;font-size:1rem;line-height:1.5rem;text-align:left;}.css-1t412wb{box-sizing:border-box;margin:8px 15px 0px 15px;cursor:pointer;}.css-hhzar2{-webkit-transition:-webkit-transform ease 0.5s;-webkit-transition:transform ease 0.5s;transition:transform ease 0.5s;}.css-t54hv4{-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-1r2j9qz{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-e1ipqs{font-size:1rem;line-height:1.5rem;padding:0px 30px 0px 0px;}.css-e1ipqs a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;}.css-e1ipqs a:hover{-webkit-text-decoration:none;text-decoration:none;}.css-1o76pdf{visibility:show;height:100%;padding-bottom:20px;}.css-1sw9s96{visibility:hidden;height:0px;}.css-1in8jot{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;font-family:’nyt-franklin’,arial,helvetica,sans-serif;text-align:left;}@media (min-width:740px){.css-1in8jot{padding:20px;width:100%;}}.css-1in8jot:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1in8jot{border:none;padding:10px 0 0;border-top:2px solid #121212;}What to Know About Covid-19 Booster ShotsThe F.D.A. has authorized booster shots for millions of recipients of the Pfizer-BioNTech, Moderna and Johnson & Johnson vaccines. Pfizer and Moderna recipients who are eligible for a booster include people 65 and older, and younger adults at high risk of severe Covid-19 because of medical conditions or where they work. Eligible Pfizer and Moderna recipients can get a booster at least six months after their second dose. All Johnson & Johnson recipients will be eligible for a second shot at least two months after the first.Yes. The F.D.A. has updated its authorizations to allow medical providers to boost people with a different vaccine than the one they initially received, a strategy known as “mix and match.” Whether you received Moderna, Johnson & Johnson or Pfizer-BioNTech, you may receive a booster of any other vaccine. Regulators have not recommended any one vaccine over another as a booster. They have also remained silent on whether it is preferable to stick with the same vaccine when possible.The C.D.C. has said the conditions that qualify a person for a booster shot include: hypertension and heart disease; diabetes or obesity; cancer or blood disorders; weakened immune system; chronic lung, kidney or liver disease; dementia and certain disabilities. Pregnant women and current and former smokers are also eligible.The F.D.A. authorized boosters for workers whose jobs put them at high risk of exposure to potentially infectious people. The C.D.C. says that group includes: emergency medical workers; education workers; food and agriculture workers; manufacturing workers; corrections workers; U.S. Postal Service workers; public transit workers; grocery store workers.Yes. The C.D.C. says the Covid vaccine may be administered without regard to the timing of other vaccines, and many pharmacy sites are allowing people to schedule a flu shot at the same time as a booster dose.“There was a value to having that as a one-dose vaccine when it first came out,” Dr. Offit said. “But I think it was always on the road to being a two-dose vaccine.”He and others suggested that people who got the Johnson & Johnson vaccine might be better served by getting a second dose of the Pfizer-BioNTech or Moderna vaccines. The F.D.A. on Wednesday updated its authorization of all three vaccines, which will allow the C.D.C.’s advisory committee to recommend this mix-and-match strategy when it meets on Thursday.At last week’s meeting, the F.D.A. advisers were shown evidence indicating that switching between two vaccine types might produce a richer immune response than boosting with the same vaccine.San Francisco has offered Pfizer-BioNTech or Moderna shots to Johnson & Johnson recipients since August, and many Americans who initially received the Johnson & Johnson vaccine have sought out booster doses of those vaccines on their own before federal agencies had endorsed them.But the F.D.A. advisers could not vote to recommend that people who initially got the Johnson & Johnson vaccine follow it up with one of the mRNA vaccines because the F.D.A. did not give them that option.“The formal vote was on the J.-&-J. booster following the J.-&-J. vaccine,” said Dr. Stanley Perlman, an immunologist and coronavirus expert at the University of Iowa. But “everybody knew that the data would show that the heterologous boost would be better.” (Heterologous refers to a shot of a different vaccine.)

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