Publisher Health

Moderna released preliminary results on Wednesday on an updated coronavirus vaccine targeting the Omicron variant, calling it “our lead candidate” to serve as a U.S. booster shot in the fall.The firm’s researchers tested a booster dose combining the original vaccine with one targeted specifically against Omicron, the variant that became dominant last winter. They found that among those with no evidence of prior coronavirus infection, the combination produced 1.75 times the level of neutralizing antibodies against Omicron as the existing Moderna vaccine did alone.While those results seem encouraging on their face, many experts worry that the virus is evolving so fast that it is outpacing the ability to modify vaccines — at least as long as the United States relies on human clinical trials for results.Moderna’s new findings, from a clinical trial involving 814 volunteers, indicate that the updated vaccine produced a significantly stronger immune response against Omicron than the existing vaccine a month after the booster shot was given. The booster shots followed three earlier doses of Moderna’s vaccine.But Omicron has been spawning subvariants for months, and some vaccine experts say what matters now is how well a new booster formulation would protect against the latest subvariants, BA.4 and BA.5, not Omicron itself. First detected in South Africa early this year, those two subvariants now account for 13 percent of new cases in the United States and are spreading fast. By some estimates, within a month they could outcompete the two other Omicron subvariants BA.2 and BA.2.12.1, which are dominant now.Moderna did not release any data on how the updated vaccine worked against BA.4 or BA.5. In a presentation Wednesday morning, Dr. Stephen Hoge, the firm’s president, said researchers were still gathering data on those and other subvariants. But he said that a very small sample, together with isolated other studies, suggested that the levels of neutralizing antibodies triggered by the updated vaccine were two to threefold lower against the BA.4 and BA.5 subvariants, compared to against Omicron.Nor can Moderna’s researchers yet say whether the reconfigured vaccine will offer more lasting protection than the existing one.The newest subvariants seem to spread even more quickly than earlier versions of Omicron, and may be better at dodging the immune system’s defenses. It is unclear whether they cause more severe disease. Dr. Anthony S. Fauci, the chief medical adviser to the White House, said in an interview Tuesday that South Africa, where BA.4 and BA.5 have been widespread, had “seen a slight uptick in hospitalizations, but I.C.U. utilization and deaths are really staying stably low.”In any case, given how fast the virus is mutating, some vaccine experts say it makes more sense to target its most recent versions, rather than forms of the virus that have already been overtaken or soon will be.The problem is that Moderna and Pfizer, the maker of the other main coronavirus vaccine in the United States, do not have enough time to run more human clinical trials and still manufacture shots before the fall, when the Biden administration is hoping to be able to offer an updated vaccine to counter what public health experts predict will be a winter surge.That might force regulators to choose updated vaccines based on data from laboratory tests and trials involving mice or other animals, rather than robust human trials. It is also possible that a new variant or subvariant of concern will appear by the fall.Outside advisers to the Food and Drug Administration are scheduled to meet June 28 to discuss which vaccine formulation would work best as a fall booster; vaccine manufacturers have said they would need to start production soon.“Of course, the final decision is always left to the F.D.A.,” Dr. Fauci said. “But what the F.D.A. will likely do is keep as many irons on the fire as they possibly can. And they may need to revert to alternative pathways of decision, which are laboratory data and possible animal data.”Asked if Americans would accept a booster formulation without lengthy human trials, he said, “People who really are very concerned about protecting themselves will.”Moderna’s trial of the vaccine targeting Omicron began in late February. The average age of the participants was 57. All volunteers had received three shots of Moderna’s existing vaccine — two shots, followed by a booster dose given an average of eight months after the second shot.About four-and-a-half months after that first booster, 377 volunteers received a second booster with the existing vaccine, while 437 received the booster designed to work against Omicron. The updated booster produced a stronger immune response among both those who had previously been infected with the virus and those who had not. Overall, those who got the updated booster had a 59 percent higher level of neutralizing antibodies than those who got the existing booster, according to data released by Moderna. Antibodies are the body’s first line of defense in warding off infection from the coronavirus. Other immune responses that also defend against Covid-19 disease were not measured; those tests are far more complex and time-consuming to conduct.Dr. Paul Burton, Moderna’s chief medical officer, described the results as highly encouraging. “We really feel like this is a sort of fundamental turning point in our fight against this virus — that we can adapt to a variant,” he said. “It works.”But John Moore, a virologist at Weill Cornell Medicine in New York, said a less than twofold increase in neutralizing antibodies over the existing vaccine is “only a modest benefit.” “Does that justify switching vaccine composition given the cost and the logistics and everything else that involved,” he asked. “That’s what the argument is going to be about.”Pfizer and BioNTech, its German partner, are also testing an Omicron-specific vaccine and are expected to release their results soon. In April, Moderna released preliminary results on a vaccine retooled to attack the Beta variant, which was first detected in late 2020. The firm said then that the combination provided a stronger defense not only against Beta, but also against the Delta and Omicron variants. But officials said they expected an Omicron-specific vaccine would be a better candidate.

Pregnant women’s use of alcohol correlates with that of their partner, a new study from the University of Eastern Finland and Kuopio University Hospital shows. Paying attention to both parents’ use of alcohol may help to prevent drinking during pregnancy, as well as fetal exposure to the adverse effects of alcohol.
Exposure to alcohol is detrimental to fetal development, and there is no known safe limit of exposure. The harmful effects of alcohol may manifest during the child’s development and growth in many ways. The risk of alcohol use during pregnancy has previously been assessed mainly on the basis of the expectant mother’s previous use of alcohol, but not on the basis of their partner’s drinking habits.
The new study looked at the alcohol consumption of 14,822 Finnish women and their partners before and during pregnancy. The study covered a total of 21,472 pregnancies between 2009 and 2018.
In 86% of the pregnancies, the expectant mother reported having used alcohol before pregnancy, and 4.5% also during pregnancy. In 25% of the pregnancies, women reported that they had stopped drinking only after learning about their pregnancy, which means that the fetus may have been exposed to alcohol in the early stages of pregnancy. However, partners generally did not reduce their alcohol consumption before or during pregnancy.
Before pregnancy, partners’ alcohol use was strongly linked to the frequency and quantity of alcohol consumed by women, how often they binge drank, and whether their drinking met the criteria for risk use. A weaker, yet significant association was observed also during pregnancy. In women who consumed alcohol during pregnancy, the quantity of alcohol used, for example, was affected by their partner’s use of alcohol.
Women who reported having used alcohol during pregnancy were usually heavy drinkers before pregnancy. Younger women had higher alcohol use risk scores before pregnancy, but during pregnancy their alcohol consumption did not differ from other age groups.
According to the researchers, the results show that, in order to protect the fetus from exposure to alcohol, both parents should reduce their alcohol consumption already when planning pregnancy. Both parents need information on the harmful effects of alcohol on the fetus, and when assessing the risk of alcohol consumption during pregnancy, the use of alcohol should be taken into account not only for the expectant mother, but also for the partner. The partner’s support may help to avoid alcohol consumption during pregnancy.
“Our findings are well in line with those from other European and American studies. There can, of course, be great local variation in maternal drinking between different sub-populations. When it comes to partners, we noticed that Finns seem to reduce their alcohol use less than what has been observed in other Nordic studies, but otherwise that, too, is in line with other Western countries,” Senior Researcher Olli Kärkkäinen from the University of Eastern Finland says.
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Scientists have, for the first time, revealed at the atomic level the structure of a protein that carries one of the body’s most important neurotransmitters into neurons.
In determining the structure of this transporter protein — one of the smallest proteins ever resolved — the researchers open new avenues to improve drugs for a wide range of debilitating conditions, including epilepsy, bipolar disorder, schizophrenia, Parkinson’s and Huntington’s diseases, anxiety and autism spectrum disorder.
The study appears June 8 in the journal Nature.
Neurons relay signals to one another by sending neurotransmitters across gaps between them, called synapses. The molecule GABA (short for gamma-amino butyric acid) is one of the most prevalent neurotransmitters in the brain.
When one neuron emits GABA, sending it out across a synapse toward a nearby neuron, GABA inhibits the activity of the receiving neuron.
But sometimes conditions can go awry, and not enough GABA reaches the receiving neuron, which may then become overactive, sending too many electrical impulses. This can cause a number of debilitating effects, including seizures.

A new tool can quickly and reliably identify the presence of Ebola virus in blood samples, according to a study by researchers at Washington University School of Medicine in St. Louis and colleagues at other institutions.
The technology, which uses so-called optical microring resonators, potentially could be developed into a rapid diagnostic test for the deadly Ebola virus disease, which kills up to 89% of infected people. Since it was discovered in 1976, Ebola virus has caused dozens of outbreaks, mostly in central and west Africa. Most notable was an outbreak that began in 2014 and killed more than 11,000 people in Guinea, Sierra Leone and Liberia; in the U.S., the virus caused 11 cases and two deaths. A rapid, early diagnostic could help public health workers track the virus’ spread and implement strategies to limit outbreaks.
The study — which also involved researchers from the University of Michigan, Ann Arbor, and Integrated Biotherapeutics, a biotech company — is published June 8 in Cell Reports Methods.
“Any time you can diagnose an infection earlier, you can allocate health-care resources more efficiently and promote better outcomes for the individual and the community,” said co-first author Abraham Qavi, MD, PhD, a postdoctoral researcher at Washington University. “Using a biomarker of Ebola infection, we’ve shown that we can detect Ebola infection in the crucial early days after infection. A few days makes a big difference in terms of getting people the medical care they need and breaking the cycle of transmission.”
Ebola virus is transmitted by contact with bodily fluids. It causes fever, body aches, diarrhea and bleeding — nonspecific symptoms that easily can be mistaken for other viral infections or for malaria. In recent years, vaccines and effective therapies for Ebola have been developed, but they are not widely available. Instead, health officials control the deadly virus by containing outbreaks. The strategy relies on quickly identifying infected people and preventing transmission by encouraging caregivers to wear protective gear.
Qavi had previously worked with Ryan C. Bailey, PhD, the Robert A. Gregg Professor of Chemistry at the University of Michigan and a co-senior author on this paper, to co-develop optical microring resonators, a kind of whispering gallery mode device used for molecular detection. The name comes from the Whispering Gallery at St. Paul’s Cathedral in London. A whisper uttered on a walkway in the dome above the nave can be heard clearly more than 100 feet away because the sound waves increase in amplitude as they bounce around the circular wall. The 18th century builders accidentally constructed a giant demonstration of the principle of acoustic resonance, in which sound waves increase in amplitude if they interact in precisely the right way. The same phenomenon occurs with light waves on a much smaller scale.

Parkinson’s disease is best-known as a disorder of movement. Patients often experience tremors, loss of balance, and difficulty initiating movement. The disease also has lesser-known symptoms that are nonmotor, including depression.
In a study of a small region of the thalamus, MIT neuroscientists have now identified three distinct circuits that influence the development of both motor and nonmotor symptoms of Parkinson’s. Furthermore, they found that by manipulating these circuits, they could reverse Parkinson’s symptoms in mice.
The findings suggest that those circuits could be good targets for new drugs that could help combat many of the symptoms of Parkinson’s disease, the researchers say.
“We know that the thalamus is important in Parkinson’s disease, but a key question is how can you put together a circuit that that can explain many different things happening in Parkinson’s disease. Understanding different symptoms at a circuit level can help guide us in the development of better therapeutics,” says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute for Brain Research at MIT.
Feng is the senior author of the study, which appears today in Nature. Ying Zhang, a J. Douglas Tan Postdoctoral Fellow at the McGovern Institute, and Dheeraj Roy, a NIH K99 Awardee and a McGovern Fellow at the Broad Institute, are the lead authors of the paper.
Tracing circuits
The thalamus consists of several different regions that perform a variety of functions. Many of these, including the parafascicular (PF) thalamus, help to control movement. Degeneration of these structures is often seen in patients with Parkinson’s disease, which is thought to contribute to their motor symptoms.

A new, detailed genetic roadmap of glaucoma — the world’s leading cause of irreversible blindness — will help researchers develop new drugs to combat the disease, by identifying potential target areas to stall or reverse vision loss.
The research, one of the largest and most detailed stem cell modelling studies reported for any disease, is published today in Cell Genomics.
By comparing stem cell models of the retinal ganglion cells of people with Primary Open Angle Glaucoma to those without the disease, more than 300 novel genetic features of these cells were uncovered.
The findings are the result of a national collaboration led by Professor Alex Hewitt (Centre for Eye Research Australia, University of Melbourne and University of Tasmania), Professor Alice Pébay and Dr Maciej Daniszewski (University of Melbourne) and Ms Anne Senabouth and Professor Joseph Powell (Garvan Institute of Medical Research).
Professor Hewitt, who is Head of Clinical Genetics at CERA, says the study will lead to a better understanding of the mechanisms that damage retinal ganglion cells and lead to the onset of glaucoma.
This will help researchers develop new drugs to combat glaucoma, by identifying potential new areas to target to stall or reverse vision loss caused by the disease.

In the early 1960s, University of Michigan alumnus Marshall Nirenberg and a few other scientists deciphered the genetic code of life, determining the rules by which information in DNA molecules is translated into proteins, the working parts of living cells.
They identified three-letter units in DNA sequences, known as codons, that specify each of the 20 amino acids that make up proteins, work for which Nirenberg later shared a Nobel Prize with two others.
Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Point mutations that alter the resulting protein sequences are called nonsynonymous mutations, while those that do not alter protein sequences are called silent or synonymous mutations.
Between one-quarter and one-third of point mutations in protein-coding DNA sequences are synonymous. Ever since the genetic code was cracked, those mutations have generally been assumed to be neutral, or nearly so.
But in a study scheduled for online publication June 8 in the journal Nature that involved the genetic manipulation of yeast cells in the laboratory, University of Michigan biologists show that most synonymous mutations are strongly harmful.
The strong nonneutrality of most synonymous mutations — if found to be true for other genes and in other organisms — would have major implications for the study of human disease mechanisms, population and conservation biology, and evolutionary biology, according to the study authors.

When someone gets an infection, most people think it’s the immune system kicking into gear when they feel some of the body’s natural defenses like a fever, chills, or fatigue. What most people don’t know is that it’s actually the brain behind all of this.
Here’s what happens: The nervous system talks to the immune system to figure out that the body has an infection and then orchestrates a series of behavioral and physiological alterations that manifest as the unpleasant symptoms of sickness. For neuroscientists, long-standing questions have been: How and where does this happens in the brain? Harvard researchers from the labs of Catherine Dulac and Xiaowei Zhuang sought the answer in the brains of mice.
In a new study published in Nature, the researchers and their collaborators describe finding a small population of neurons near the base of the brain that can induce symptoms of sickness, including fever, appetite loss, and warm seeking behavior.
The neurons, which have not been previously described, are found in an area of the hypothalamus, a part of the brain known for controlling key homeostatic functions that keep the body in a balanced, healthy state. The researchers found these neurons have receptors that are capable of directly detecting molecular signals coming from the immune system, an ability most neurons don’t have.
“It was important for us to establish this general principle that the brain can even sense these immune states,” said Jessica Osterhout, a postdoctoral researcher in the Dulac Lab and the study’s lead author. “This was poorly understood before.”
The researchers found that the key area of the hypothalamus is located right next to a permeable section of the brain called the blood-brain barrier, which helps circulates blood to the brain.

Scientists discovered years ago that newborn infants depend upon immune components transferred from their mothers to survive the onslaught of pathogens that begin invading their bodies as soon as they are born. Eventually, children develop their own immune systems, built through surviving natural exposures to viruses and bacteria, and augmented by a phalanx of well-established childhood vaccines. But in the meantime, it’s one of a mother’s most important gifts that keeps their babies safe: antibodies.
Now, a far-reaching study published June 8, 2022, in Nature, provides a surprising explanation of how those early days of mother-provided immunity actually work-and what that information could mean for preventing death and disability from a wide range of infectious diseases. The findings suggest that researchers may be able to mimic the amped-up antibodies that expecting mothers produce to create new drugs to treat diseases as well as improved vaccines to prevent them.
“For many years, scientists believed that antibodies cannot get inside cells. They don’t have the necessary machinery. And so, infections caused by pathogens that live exclusively inside cells were thought to be invisible to antibody-based therapies,” says Sing Sing Way, MD, PhD, Division of Infectious Diseases at Cincinnati Children’s. “Our findings show that pregnancy changes the structure of certain sugars attached to the antibodies, which allows them to protect babies from infection by a much wider range of pathogens.”
“The maternal-infant dyad is so special. It’s the intimate connection between a mother and her baby,” says John Erickson, MD, PhD, Division of Neonatology, and first-author of the study.
Both Way and Erickson are part of Cincinnati Children’s Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns.
Erickson continues, “This special connection starts when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborns babies. I believe these findings also will have far-reaching implications for antibody-based therapies in other fields.”
How mothers make super antibodies

Using advanced microscopy techniques, researchers at Karolinska Institutet and Stockholm University in Sweden have visualized in unprecedented detail the machinery that the cells’ powerhouses, the mitochondria, use to form their proteins. The results, which are published in Nature, raise hopes of more specific antibiotics and new cancer drugs in the future.
The mitochondria are the cells’ powerhouses that convert energy locked in our food into a functional “energy currency” for the cells. They also have their own protein synthesis factories called ribosomes, which have a different appearance to those found in the cellular cytoplasm. However, little has been known about how the mitochondrial ribosomes are produced — until now.
“We were hoping to obtain a single snapshot of the mitoribosomal large subunit assembly, but our data revealed much more unexpected surprises,” says the study’s joint first author Anas Khawaya, postdoc at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. “These observations present opportunities to discover the full extent of crosstalk between mitoribosomal assembly and other aspects of mitochondrial function.”
Using a technique called cryogenic electron microscopy, the researchers were able to depict important key players of the complex machinery that manufactures ribosomes. One finding was that a component called ribosome-binding factor A (RBFA) orchestrates the process. The ribosome is made up of two halves, not unlike a hamburger bun. The researchers’ analyses show that a protein called mS37 signals that these two parts can be joined and are ready to start protein synthesis.
Clinical potential
The results are an example of basic cell biology research, but the new knowledge can also give rise to medical advances, such as more targeted antibiotics. Mitochondria are similar to bacteria and the antibiotics that currently attack a bacterium’s ability to form proteins also affect our mitochondria.
“Whilst the mechanisms of bacterial and cytosolic translation have been studied for decades, we are only now starting to uncover how mitochondria produce proteins,” says Joanna Rorbach, principal researcher and group leader at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. “Understanding the differences between how bacteria and mitochondria produce their ribosomes could allow us to design better and more targeted antibiotics.”
The study has been led by Joanna Rorbach together with Alexey Amunts and his research group at the Department of Biochemistry and Biophysics at Stockholm University.
Cancer is another future target. Unlike healthy cells, cancer cells grow quickly and divide often, a process that requires the formation of a large number of new proteins.
“One possible approach is to actively inhibit the cancer cells’ mitochondrial ribosomes,” Joanna Rorbach says.
The study was supported by grants from the Max Planck Society, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the European Research Council, the Swedish Foundation for Strategic Research, the Marie Sklodowska Curie Initiative and Karolinska Institutet.
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