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Study shows why second dose of COVID-19 vaccine shouldn’t be skipped

The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by investigators at the Stanford University School of Medicine.

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The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by investigators at the Stanford University School of Medicine.

The finding strongly supports the view that the second shot should not be skipped.

“Despite their outstanding efficacy, little is known about how exactly RNA vaccines work,” said Bali Pulendran, PhD, professor of pathology and of microbiology and immunology. “So we probed the immune response induced by one of them in exquisite detail.”

The study, published in Nature, was designed to find out exactly what effects the vaccine, marketed by Pfizer Inc., has on the numerous components of the immune response.

The researchers analyzed blood samples from individuals inoculated with the vaccine. They counted antibodies, measured levels of immune-signaling proteins and characterized the expression of every single gene in the genome of 242,479 separate immune cells’ type and status.

“The world’s attention has recently been fixed on COVID-19 vaccines, particularly on the new RNA vaccines,” said Pulendran, the Violetta L. Horton Professor II.

He shares senior authorship of the study with Kari Nadeau, MD, PhD, the Naddisy Foundation Professor of Pediatric Food, Allergy, Immunology, and Asthma and professor of pediatrics, and Purvesh Khatri, PhD, associate professor of biomedical informatics and of biomedical data science. The study’s lead authors are Prabhu Arunachalam, PhD, a senior research scientist in Pulendran’s lab; medical student Madeleine Scott, PhD, a former graduate student in Khatri’s lab; and Thomas Hagan, PhD, a former postdoctoral scholar in Pulendran’s Stanford lab and now an assistant professor at the Yerkes National Primate Research Center in Atlanta.

Uncharted territory

“This is the first time RNA vaccines have ever been given to humans, and we have no clue as to how they do what they do: offer 95% protection against COVID-19,” said Pulendran.

Traditionally, the chief immunological basis for approval of new vaccines has been their ability to induce neutralizing antibodies: individualized proteins, created by immune cells called B cells, that can tack themselves to a virus and block it from infecting cells.

“Antibodies are easy to measure,” Pulendran said. “But the immune system is much more complicated than that. Antibodies alone don’t come close to fully reflecting its complexity and potential range of protection.”

Pulendran and his colleagues assessed goings-on among all the immune cell types influenced by the vaccine: their numbers, their activation levels, the genes they express and the proteins and metabolites they manufacture and secrete upon inoculation.

One key immune-system component examined by Pulendran and his colleagues was T cells: search-and-destroy immune cells that don’t attach themselves to viral particles as antibodies do but rather probe the body’s tissues for cells bearing telltale signs of viral infections. On finding them, they tear those cells up.

In addition, the innate immune system, an assortment of first-responder cells, is now understood to be of immense importance. It’s the body’s sixth sense, Pulendran said, whose constituent cells are the first to become aware of a pathogen’s presence. Although they’re not good at distinguishing among separate pathogens, they secrete “starting gun” signaling proteins that launch the response of the adaptive immune system — the B and T cells that attack specific viral or bacterial species or strains. During the week or so it takes for the adaptive immune system to rev up, innate immune cells perform the mission-critical task of holding incipient infections at bay by gobbling up — or firing noxious substances, albeit somewhat indiscriminately, at — whatever looks like a pathogen to them.

A different type of vaccine

The Pfizer vaccine, like the one made by Moderna Inc., works quite differently from the classic vaccines composed of live or dead pathogens, individual proteins or carbohydrates that train the immune system to zero in on a particular microbe and wipe it out. The Pfizer and Moderna vaccines instead contain genetic recipes for manufacturing the spike protein that SARS-CoV-2, the virus that causes COVID-19, uses to latch on to cells it infects.

In December 2020, Stanford Medicine began inoculating people with the Pfizer vaccine. This spurred Pulendran’s desire to assemble a complete report card on the immune response to it.

The team selected 56 healthy volunteers and drew blood samples from them at multiple time points preceding and following the first and second shots. The researchers found that the first shot increases SARS-CoV-2-specific antibody levels, as expected, but not nearly as much as the second shot does. The second shot also does things the first shot doesn’t do, or barely does.

“The second shot has powerful beneficial effects that far exceed those of the first shot,” Pulendran said. “It stimulated a manifold increase in antibody levels, a terrific T-cell response that was absent after the first shot alone, and a strikingly enhanced innate immune response.”

Unexpectedly, Pulendran said, the vaccine — particularly the second dose — caused the massive mobilization of a newly discovered group of first-responder cells that are normally scarce and quiescent.

First identified in a recent vaccine study led by Pulendran, these cells — a small subset of generally abundant cells called monocytes that express high levels of antiviral genes — barely budge in response to an actual COVID-19 infection. But the Pfizer vaccine induced them.

This special group of monocytes, which are part of the innate museum, constituted only 0.01% of all circulating blood cells prior to vaccination. But after the second Pfizer-vaccine shot, their numbers expanded 100-fold to account for a full 1% of all blood cells. In addition, their disposition became less inflammatory but more intensely antiviral. They seem uniquely capable of providing broad protection against diverse viral infections, Pulendran said.

“The extraordinary increase in the frequency of these cells, just a day following booster immunization, is surprising,” Pulendran said. “It’s possible that these cells may be able to mount a holding action against not only SARS-CoV-2 but against other viruses as well.”

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Unlocking the science of sleep: How rest enhances language learning

Getting eight hours of sleep every night helps the brain to store and learn a new language.

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Sleep is critical for all sorts of reasons, but a team of international scientists has discovered a new incentive for getting eight hours of sleep every night: it helps the brain to store and learn a new language.

A study led by the University of South Australia (UniSA) and published in the Journal of Neuroscience has revealed that the coordination of two electrical events in the sleeping brain significantly improves our ability to remember new words and complex grammatical rules.

In an experiment with 35 native English-speaking adults, researchers tracked the brain activity of participants learning a miniature language called Mini Pinyin that is based on Mandarin but with similar grammatical rules to English.

Half of the participants learned Mini Pinyin in the morning and then returned in the evening to have their memory tested. The other half learned Mini Pinyin in the evening and then slept in the laboratory overnight while their brain activity was recorded. Researchers tested their progress in the morning.

Those who slept performed significantly better compared to those who remained awake.

Lead researcher  Dr Zachariah Cross, who did his PhD at UniSA but is now based at Northwestern University in Chicago, says sleep-based improvements were linked to the coupling of slow oscillations and sleep spindles – brainwave patterns that synchronise during NREM sleep.

“This coupling likely reflects the transfer of learned information from the hippocampus to the cortex, enhancing long-term memory storage,” Dr Cross says.

“Post-sleep neural activity showed unique patterns of theta oscillations associated with cognitive control and memory consolidation, suggesting a strong link between sleep-induced brainwave co-ordination and learning outcomes.”

UniSA researcher Dr Scott Coussens says the study underscores the importance of sleep in learning complex linguistic rules.

“By demonstrating how specific neural processes during sleep support memory consolidation, we provide a new perspective on how sleep disruption impacts language learning,” Dr Coussens says. “Sleep is not just restful; it’s an active, transformative state for the brain.”

The findings could also potentially inform treatments for individuals with language-related impairments, including autism spectrum disorder (ASD) and aphasia, who experience greater sleep disturbances than other adults.

Research on both animals and humans shows that slow oscillations improve neural plasticity – the brain’s ability to change and adapt in response to experiences and injury.

“From this perspective, slow oscillations could be increased via methods such as transcranial magnetic stimulation to accelerate aphasia-based speech and language therapy,” Dr Cross says.

In future, the researchers plan to explore how sleep and wake dynamics influence the learning of other complex cognitive tasks.

“Understanding how the brain works during sleep has implications beyond language learning. It could revolutionize how we approach education, rehabilitation, and cognitive training.”

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Home and neighborhood environments impact sedentary behavior in teens globally

Adolescents worldwide are spending an average of 8 to 10 hours per day engaging in sedentary activities such as watching television, using electronic devices, playing video games and riding in motorized vehicles.

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The World Health Organization recommends no more than two to three hours per day of sedentary time for youth. However, adolescents worldwide are spending an average of 8 to 10 hours per day engaging in sedentary activities such as watching television, using electronic devices, playing video games and riding in motorized vehicles, according to a multinational study published in the Nov. 29, 2024 issue of the International Journal of Behavioral Nutrition and Physical Activity.

The most notable finding of the study, led by principal investigator James F. Sallis, Ph.D., distinguished professor at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego, and colleagues from 14 countries, found that simply having a personal social media account was linked with higher total sedentary time in both males and females. Social media was also related to more self-reported screen time.

“Although there is great concern about negative effects of social media on youth mental health, this study documents a pathway for social media to harm physical health as well,” said Sallis, who is also a professorial fellow at the Australian Catholic University.

“These findings are concerning, as excessive sedentary behavior has been linked to a range of health problems, including obesity, diabetes and mental health issues.”

Researchers analyzed accelerometer data from 3,982 adolescents aged 11 to 19 and survey measures of sedentary behavior from 6,302 participants in the International Physical Activity and the Environment Network (IPEN) Adolescent Study, which covered 15 geographically and culturally diverse countries across six continents.

The number of electronic devices within a home, how many adolescents had their own social media accounts and neighborhood walkability were significantly different across countries.

For example, adolescents from India had an average of 1.2 electronic devices in the bedroom and 0.5 personal electronic devices, while the average number of such devices in Denmark was 4.2 and 2.3, respectively. In India and Bangladesh, fewer than 30% of adolescents reported having their own social media account, compared to higher socio-economic status countries where it was over 90%.

Parents reporting on walkability identified Australia as having high access to parks, while Nigerian parents reported no access, and parents in Bangladesh and India reported poor access. Traffic was a concern among parents in Brazil, Malaysia, Bangladesh, India, and Israel, and concerns about crime were high in the first three countries.

Adolescents who reported less recreational screen time lived in walkable neighborhoods and had better perceptions of safety from traffic and crime than others. Girls who lived in neighborhoods designed to support physical activity were less likely to be sedentary.

Despite differences in culture, built environments and extent of sedentary time, patterns of association were generally similar across countries, said the study’s lead author Ranjit Mohan Anjana, M.D., Ph.D., of Dr. Mohan’s Diabetes Specialties Centre and Madras Diabetes Research Foundation in India.

“Together, parents, policymakers and technology companies can work together to reduce access to screens, limit social media engagement and promote more physical activity, thus helping adolescents develop healthier habits and reduce their risk of chronic diseases,” said Anjana.

The study’s findings have significant implications for public health policy and highlight the need for further research into the causes and consequences of sedentary behavior among teenagers.

Countries involved in study: Australia, Bangladesh, Belgium, Brazil, China, Czechia, Denmark, India, Israel, Malaysia, Nigeria, Portugal, Spain and United States.

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People using vapes and cigarettes are less likely to quit and often switch to just smoking

Over a period of four to eight months, 30% of dual users switched to cigarettes only. Between eight and 16 months, 47% of dual users switched to cigarettes only. Between 16 and 24 months, the proportion was 58% and after 24 to 48 months, the proportion was 55%.

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People who use both vapes and cigarettes are less likely to quit compared to people who only smoke or only vape, according to a study published in ERJ Open Research. Instead, the research suggests that over time, most of these ‘dual users’ tend to revert to only smoking cigarettes.

The researchers say their findings suggest that taking up vaping while continuing to smoke will probably not help people to stop smoking.

The study, by researchers from Germany, the USA and Denmark, was authored by Josef Hamoud from the University Medical Center Göttingen, Germany. It is a systematic review and meta-analysis, meaning researchers reviewed all existing research on people using both vapes and cigarettes and combined the data into one study.

Hamoud said: “Vaping has become widespread among adolescents and adults worldwide. Given the extensive marketing of vapes as healthier alternatives to conventional smoking, they have gained popularity among people trying to quit smoking. Some people are using them in addition to their conventional cigarettes, classifying them as dual users.

“There is still a lot we don’t know about the long-term health effects of vaping. However, credible studies have already delivered concerning results indicating that dual use might be even more harmful than conventional smoking.”

The review brings together 16 individual studies looking at whether groups of dual users went on to quit smoking, switch to vaping only, switch to smoking only or continue dual use over time. The analyses incorporate data on up to 9,337 people including 2,432 dual users.

When researchers compared dual users with people who only smoked cigarettes or only vaped, they found that dual users were less likely to quit completely. Over time, the analysis showed that the majority of dual users reverted to smoking conventional cigarettes.

The proportion of dual users who quit completely was 3% over a period of four to eight months, 5% by eight to 16 months, 13% by 16 to 24 months and 24% by 24 to 48 months. This compares to 6%, 7%, 17% and 25% respectively over the same time periods in people who only smoke and 8%, 19%, 26% and 35% respectively in people who only vape.

Over a period of four to eight months, 30% of dual users switched to cigarettes only. Between eight and 16 months, 47% of dual users switched to cigarettes only. Between 16 and 24 months, the proportion was 58% and after 24 to 48 months, the proportion was 55%.

Most dual users continued to use cigarettes across the time periods. Combining those who continued dual use with those who transitioned to smoking only, the total proportion using cigarettes ranged from 90% to 63%.

The researchers also point out that over the medium term (eight to 16 months), 38% of dual users were still using both vapes and cigarettes. “This cannot be considered a simple ‘transitional state’, but rather a risk for prolonged double exposure,” Hamoud said.

He continued: “Given these findings, we believe that dual use might prove to be a major hinderance in achieving smoking abstinence and this practice should not be recommended for treating nicotine addiction. In addition, while long term health effects of vapes need to be studied further, the double exposure to large amounts of nicotine and toxicants from both conventional cigarettes and vapes are a great concern for public health.”

The researchers say that because they were combining several studies, each with a slightly different approach, it was not possible to categorise different types of dual use, such as people who mostly smoke but occasionally vape.

Hamoud added: “While it may have been argued that heavy smokers might benefit from dual use by reducing their daily cigarette consumption, the high nicotine content of vapes adds to the risk of continued nicotine addiction. Future studies must further stratify dual-use groups to investigate the health implications over time.”

Dr Filippos Filippidis is Chair of the European Respiratory Society Tobacco Control Committee, a reader in public health at Imperial College London, UK, and was not involved in the research. He said: “We know that vaping is commonplace and that many people use e-cigarettes as well as cigarettes, often in the hopes of cutting down on smoking or quitting the habit. This large study examined all existing evidence on dual users, and it showed that, for most people, this is not a stepping stone to quitting”.

“Nicotine in vapes is highly addictive, so we need to do all we can to discourage non-smokers from starting to vape. E-cigarettes may have a role in smoking cessation for some people, but we need to make sure appropriate support is freely available to help people to quit, as it’s clear that many end up being dual users, which can actually undermine smoking cessation attempts.”

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