In a 2022 survey of 3,000 U.S. adults, more than one-third of respondents reported that on most days, they feel “completely overwhelmed[1]” by stress. At the same time, a growing body of research is documenting the negative health consequences of higher stress levels[2], which include increased rates of cancer, heart disease, autoimmune conditions and even dementia[3].
Assuming people’s daily lives are unlikely to get less...
Vaccination of pregnant women has been linked to a drop in newborns being admitted to hospital with a serious lung infection, research suggests.
Researchers found the respiratory syncytial virus (RSV) vaccine, introduced across the UK in late summer 2024, led to a 72 percent reduction in babies hospitalized with the virus if mothers were vaccinated.
The findings are the first to show the real-world effectiveness of the vaccine in pregnant women in the UK.
Uptake of the jab among pregnant women could help to limit the number of sick babies each winter, reducing hospital pressures, experts say.
RSV is a common virus that causes coughs and colds but can lead to a severe lung infection called bronchiolitis, which can be dangerous in babies, with some requiring admission to intensive care. The virus is the main infectious cause of hospitalization for babies in the UK and globally.
Receiving the vaccine during pregnancy helps to protect both mother and baby. Antibodies - proteins which help to prevent the virus causing severe infection - produced by the mother in response to the vaccine are passed to the fetus, providing protection from severe RSV for the first six months after birth.
The research team, led by the Universities of Edinburgh and Leicester, recruited 537 babies across England and Scotland who had been admitted to hospital with severe respiratory disease in the winter of 2024-2025, the first season of vaccine implementation. 391 of the babies tested positive for RSV.
Mothers of babies who did not have RSV were two times more likely to have received the vaccine before delivery than the mothers of RSV-positive babies - 41 percent compared with 19 percent.
Receiving the vaccine more than 14 days before delivery offered a higher protective effect, with a 72 percent reduction in hospital admissions compared with 58 percent for infants whose mothers were vaccinated at any time before delivery.
Experts recommend getting vaccinated as soon as possible from 28 weeks of pregnancy to provide the best protection, as this allows more time for the mother to generate and pass on protective antibodies to the baby, but the jab can be given up to birth.
Previous research has found that only half of expectant mothers in England and Scotland are currently receiving the RSV vaccine, despite its high success at preventing serious illness.
The findings highlight the importance of raising awareness of the availability and effectiveness of the new vaccine to help protect babies, experts say.
The study is published in the journal The Lancet Child and Adolescent Health. The research collaboration also included the Universities of Bristol, Oxford, Queen's University Belfast, UCL and Imperial College London and 30 hospitals across England and Scotland.
The study was funded by the Innovative Medicines Initiative (IMI) Respiratory Syncytial Virus Consortium in Europe (RESCEU), the Wellcome Trust and National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Respiratory Infections, Imperial College London.
Dr Thomas Williams, study lead from the University of Edinburgh's Institute for Regeneration and Repair, and Paediatric Consultant at the Royal Hospital for Children and Young People in Edinburgh, said: "With the availability of an effective RSV vaccine shown to significantly reduce the risk of hospitalization in young infants in the UK, there is an excellent opportunity for pregnant women to get vaccinated and protect themselves and their infants from RSV bronchiolitis this coming winter."
Professor Damian Roland from the Leicester Hospitals and University and Consultant in Paediatric Emergency Medicine, said: "Our work highlights the value of vaccination and in keeping with the treatment to prevention principle of the NHS 10 Year plan we would ask all health care systems to consider how they will optimize the roll out of RSV vaccination for mothers."
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As millions of people know firsthand, the most common side effect of mRNA vaccines like the COVID-19 shot is inflammation: soreness, redness and a day or two of malaise. But what if mRNA vaccines could be redesigned to sidestep that response altogether?
In a new paper in Nature Biomedical Engineering, researchers at the University of Pennsylvania show that tweaking the structure of the ionizable lipid, a key component of the lipid nanoparticles (LNPs) that deliver mRNA, not only reduces inflammation but also boosts vaccine effectiveness for preventing or treating a range of diseases, from COVID-19 to cancer.
The key change? Adding phenol groups, chemical compounds with anti-inflammatory properties famously found in foods like olive oil. "By essentially changing the recipe for these lipids, we were able to make them work better with fewer side effects," says Michael J. Mitchell, Associate Professor in Bioengineering (BE) and the paper's senior author. "It's a win-win."
Revising the Recipe
Until now, the ionizable lipids in LNPs -- one of four types of lipids in LNPs, and arguably the most important -- have largely been synthesized using chemical reactions that combine two components into a new molecule, much like two halves of a sandwich coming together.
"Because these processes have been so successful, there hasn't been much effort to look for alternatives," says Ninqiang Gong, a former postdoctoral fellow in the Mitchell Lab and co-first author of the paper.
Looking back at the history of chemistry, the team found an alternative approach: the Mannich reaction, named after the German chemist who discovered it more than a century ago.
Rather than two components, the Mannich reaction combines three precursors, allowing for a greater variety of molecular outcomes. "We were able to create hundreds of new lipids," says Gong.
Exploring that "library" of lipids led the team to discover that adding a phenol group -- a combination of hydrogen and oxygen connected to a ring of carbon molecules -- substantially reduced inflammation.
"It's kind of like the secret sauce," says Gong. "The phenol group not only reduces the side effects associated with LNPs, but improves their efficacy."
The Power of Phenols
Previous studies have found that phenol-containing compounds reduce inflammation by negating the harmful effects of free radicals, molecules with unpaired electrons that can disrupt the body's chemistry.
Too many free radicals and too few antioxidants result in "oxidative stress," which degrades proteins, damages genetic material and can even kill cells.
By checking various markers associated with oxidative stress, the researchers compared the inflammatory effects of LNPs formulated using different lipids.
"The best-performing LNP, which we built using a phenol-containing ionizable lipid produced by the Mannich reaction, actually caused less inflammation," says Emily Han, a doctoral student in BE and co-author of the paper.
Less Inflammation, Higher Performance
With these encouraging signs of reduced inflammation, the researchers next tested whether the new lipids also improved vaccine performance.
Across multiple experiments, C-a16 LNPs, which incorporated the most anti-inflammatory lipid, outperformed LNPs used in on-the-market mRNA technologies.
"Lowering oxidative stress makes it easier for LNPs to do their job," says Dongyoon Kim, a postdoctoral fellow in the Mitchell Lab and co-first author of the paper.
C-a16 LNPs not only produced longer-lasting effects, but also improved the efficacy of gene-editing tools like CRISPR and the potency of vaccines for treating cancer.
Fighting Genetic Disease, Cancer and COVID-19
To test how well the new C-a16 lipids worked in an animal model, the researchers first used them to deliver into cells the gene that makes fireflies glow -- a classic experiment for checking the strength of genetic instructions.
The glow in mice was about 15 times brighter compared to the LNPs used in Onpattro, an FDA-approved treatment for hereditary transthyretin amyloidosis (hATTR), a rare genetic liver disease.
The C-a16 lipids also helped gene-editing tools like CRISPR do a better job fixing the faulty gene that causes hATTR. In fact, they more than doubled the treatment's effectiveness in a mouse model compared to current delivery methods.
In cancer treatments, the results were just as striking. In an animal model of melanoma, an mRNA cancer treatment delivered with C-a16 lipids shrank tumors three times more effectively than the same treatment delivered with the LNPs used in the COVID-19 vaccines. The new lipids also gave cancer-fighting T cells a boost, helping them recognize and destroy tumor cells more efficiently -- and with less oxidative stress.
Finally, when the team used the C-a16 lipids for preparing COVID-19 mRNA vaccines, the immune response in animal models was five times stronger than with standard formulations.
"By causing less disruption to cellular machinery, the new, phenol-containing lipids can enhance a wide range of LNP applications," says Kim.
Old Chemistry, New Frontiers
Besides investigating the immediate potential of the new lipids to reduce side effects in mRNA vaccines, the researchers look forward to exploring how overlooked chemical processes like the Mannich reaction can unlock new LNP-enhancing recipes.
"We tried applying one reaction discovered a century ago, and found it could drastically improve cutting-edge medical treatments," says Mitchell. "It's exciting to imagine what else remains to be rediscovered."
This study was conducted at the University of Pennsylvania School of Engineering and Applied Science (Penn Engineering) and the Perelman School of Medicine (Penn Medicine), and was supported by a U.S. National Institutes of Health (NIH) Director's New Innovator Award (DP2 TR002776), a Burroughs Wellcome Fund Career Award at the Scientific Interface (CASI), a U.S. National Science Foundation CAREER Award (CBET-2145491), the American Cancer Society (RSG-22-122-01-ET), two US National Science Foundation Graduate Research Fellowships (DGE 1845298, DGE 1845298), a GEM Fellowship, and the NIH/National Cancer Institute Pre-doc to Post-doc Transition Award (F99 CA284294).
Additional co-authors include Rohan Palanki, Qiangqiang Shi, Xuexiang Han, Lulu Xue, Junchao Xu and Christian G. Figueroa-Espada of Penn Engineering; Drew Weissman, Mohamad-Gabriel Alameh, Rakan El-Mayta and Garima Dwivedi of Penn Medicine; and Zilin Meng, Tianyu Luo and Jinghong Li of USTC.