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Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) have completed a successful Phase 1 clinical trial of a novel vaccine designed to protect against both typhoid fever and invasive non-typhoidal Salmonella–two major causes of illness and death among children in sub-Saharan Africa.

Results were published today in the journal Nature Medicine.

The investigational Trivalent Salmonella Conjugate Vaccine (TSCV) includes sugar molecules taken from the outer coating of the Salmonella typhi bacteria that cause typhoid and the two most common types of invasive Salmonella infections that are not associated with typhoid caused by Salmonella enterica. These sugars are attached to special proteins that help the body recognize and respond to the bacteria more effectively.

In the randomized, placebo-controlled Phase 1 trial, 22 healthy adults in the US received either a low dose (6.25 µg) or high dose (12.5 µg) of TSCV, or a placebo shot. The vaccine was found to be safe and well-tolerated, with only mild, short-lived injection site pain reported. Importantly, 100 percent of the vaccine recipients developed strong immune responses to all three polysaccharide components, while none of the placebo recipients did.

“These results are highly encouraging,” said study lead investigator Wilbur Chen, MD, MS, Professor of Medicine at UM School of Medicine and Chief of the Adult Clinical Studies section within CVD. “They show that TSCV has the potential to protect children in regions where both typhoid and salmonella are endemic and deadly.”

The vaccine also has the potential to protect Americans against Salmonella infections, one of the leading causes of foodborne illness. Every year, bacteria from raw or undercooked chicken and eggs and contaminated produce cause 1.35 million Salmonella infections in the US and more than 26,000 hospitalizations, according to the Centers for Disease Control and Prevention. The serotypes targeted by the TSCV vaccine are among the most common in US infections.

In fact, some study participants showed pre-existing antibody responses, suggesting prior exposure to the bacteria via foodborne illness. Such priming might have led to stronger and longer-lasting immunity in the adult study volunteers, though researchers remain optimistic about the vaccine’s effectiveness in infants and young children in endemic regions.

The vaccine triggered a strong and balanced immune response, including long-lasting antibodies—even at lower doses. It also activated a specific immune defense involving white blood cells that help clear infections, which hadn’t been seen before with one of the vaccine’s protein components. These findings suggest the vaccine could offer both gut-level and whole-body protection against Salmonella.

“These findings provide a strong foundation for future studies,” said study co-author Myron Levine, MD, DTPH, professor emeritus at UM School of Medicine and CVD founding director. “We plan to explore broader functional assays to identify correlates of protection and evaluate TSCV’s performance in young children—the population most vulnerable to these diseases.”

The vaccine was developed in collaboration with Bharat Biotech International Limited (BBIL), building on their WHO-prequalified Typbar TCV™ platform.

“In 2017, sub-Saharan Africa saw over 420,000 cases of Salmonella disease and 66,000 deaths, primarily among children,” said Mark T. Gladwin, MD, Dean of the UM School of Medicine. “Typhoid fever caused an additional 650,000 cases and nearly 9,000 deaths in the region. A single vaccine that protects against both could be a game-changer for global pediatric health.”

Reference:

Chen, W.H., Barnes, R.S., Sikorski, M.J. et al. A combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine in healthy adults: a randomized, placebo-controlled phase 1 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-04003-z

A University of Arizona research team will receive nearly $2.7 million from the NIH’s Common Fund Venture Program to advance next-generation imaging technologies that allow deeper, clearer views inside the body without the need for invasive procedures.

The U of A team, led by Florian Willomitzer in the James C. Wyant College of Optical Sciences and Dr. Clara Curiel-Lewandrowski in the U of A Comprehensive Cancer Center, is one of only four groups nationwide to receive funding through the “Advancing Non-Invasive Optical Imaging Approaches for Biological Systems” initiative. The final award amount is pending successful completion of milestones and availability of funds.

The U of A research group will develop optical technology capable of peering deep into biological tissues, such as skin or soft tissue linings inside the body. The approach could be used to image skin cancers, the most prevalent malignancy worldwide, to help physicians assess tumor invasion and monitor treatment response.

The noninvasive approach is based on synthetic wavelength imaging, or SWI, which uses two separate illumination wavelengths to computationally generate one virtual, “synthetic” imaging wavelength. Due to the longer, synthetic wavelength, the signal is more resistant to light scattering inside tissue. At the same time, researchers can take advantage of the higher contrast information provided by the original illumination wavelengths.

“This project specifically focuses on nonmelanoma skin cancers, such as basal cell carcinoma or squamous cell carcinoma,” said principal investigator and project lead Willomitzer, an associate professor of optical sciences. “Those skin cancers can display significantly different imaging contrast properties than melanoma, which poses a unique challenge to the development of new ‘deep’ imaging technologies.”

Current skin cancer imaging methods, such as confocal microscopy or optical coherence tomography, use optical light with wavelengths in the visible to near-infrared spectrum, according to Willomitzer. They offer superior contrast and resolution at shallow tissue depths, but their relatively short imaging wavelengths make them susceptible to light scattering deep inside biological tissue. Longer wavelength methods, like ultrasound or hybrid approaches, can image deeper layers, but they often lack resolution or sufficient contrast needed for certain cancer types.

“From a translational standpoint, this limitation is particularly important,” said Curiel-Lewandrowski, the other principal investigator, chair of the Department of Dermatology at the College of Medicine – Tucson and co- director of the Skin Cancer Institute at the U of A Cancer Center. “Patients with nonmelanoma skin cancers often present with lesions that vary widely in size, depth and pattern of invasion.”

According to Curiel-Lewandrowski, imaging tools must be versatile enough to accurately assess tumor margins at the time of diagnosis, while also being robust and reliable enough to monitor how lesions respond over the course of treatment.

“To achieve this, we need tunable imaging capabilities that balance depth penetration with resolution and imaging contrast – something that current technologies cannot reliably provide,” she said.

The NIH’s Common Fund Advancing Non-Invasive Optical Imaging Approaches for Biological Systems Venture Initiative seeks to overcome these and other limitations through technology development that will allow light to deeply image through tissue non-invasively at high resolution. Enhanced imaging techniques can make possible earlier detection of health conditions, more precise evaluation of cellular and tissue health, and advancements in non-invasive procedures to replace surgery. The NIH initiative seeks to produce highly detailed images that can reveal structures ranging from individual cells to larger features of living tissues. It also aims to record rapid biological processes, such as muscle contractions and pulse, with enough speed to capture them in real time.

“Synthetic wavelength imaging’s resilience to scattering in deep tissue while preserving high tissue contrast at the optical carrier wavelengths is a rare combination,” Willomitzer explained. “By pairing this property with advanced computational evaluation algorithms, our approach aims to break free from the conventional resolution-depth-contrast tradeoff.”

The team aims to bridge a critical gap in skin cancer care by advancing this new technology, Curiel-Lewandrowski said.

“Our goal is to translate these imaging advances into clinical practice,” she said. “If we can detect invasive lesions earlier, define tumor margins more precisely and monitor response to non-invasive treatments in real time, we can maximize the effectiveness of emerging therapeutic approaches. This will also allow us to tailor intervention length and dosing individually to each patient.”

Co-investigator Jennifer Barton, who holds the Thomas R. Brown distinguished chair in biomedical engineering, said, “This project will significantly advance non-invasive optical approaches for biomedical imaging, and exemplifies the exciting developments possible when U of A’s health sciences, engineering and optical sciences investigators collaborate.”

Other team members on the project funded by this NIH award (1UG3DA065139-01) include Sally Dickinson, a research associate professor of pharmacology at the Cancer Center, and Muralidhar Madabhushi Balaji, a postdoctoral research associate in Willomitzer’s group at the Wyant College of Optical Sciences.

“We anticipate that our advancements will facilitate the first clinical demonstration of synthetic wavelength imaging in the critical, unmet need of assessing non-melanoma skin cancers,” Curiel-Lewandrowski said.

“If we are successful,” Willomitzer said, “the wide tunability of the synthetic wavelength opens up additional potential avenues in biomedical imaging through strongly scattering tissue for our approach, such as novel detection methods for breast cancer or imaging deep inside the human brain.”

Women performed best on cognitive tests during ovulation but physical activity level had a stronger influence on brain function, according to a new study from researchers at UCL.

The study, published in Sports Medicine – Open, explored how the different phases of the menstrual cycle and physical activity level affected performance on a range of cognitive tests designed to mimic mental processes used in team sports and everyday life, such as the accurate timing of movements, attention, and reaction time.

The team found that women had the fastest reaction times and made the fewest errors on the day of ovulation, when the ovaries release an egg ready to be fertilised (and when women’s fertility is at its peak).

But while cognitive performance fluctuated across the menstrual cycle, much greater differences were observed between those who were active and those who weren’t. Compared to active participants, inactive participants had reaction times on average around 70 milliseconds slower and made around three times as many impulsive errors, regardless of cycle phase.

The researchers say the findings are particularly relevant to women’s sport, where slightly quicker reaction times of around 20 milliseconds may make the difference between sustaining or avoiding an injury like concussion. Previous research on elite athletes has suggested injuries are more common at certain points during the menstrual cycle, and the authors say that these changes in cognition might partially explain this occurrence.

However, while a difference of 20 milliseconds is likely to be inconsequential in everyday life, the much larger difference between active and inactive groups is more significant, where 70 milliseconds could determine whether we regain balance after tripping over an obstacle or not.

Dr Flaminia Ronca, lead author of the study from UCL Surgery and Interventional Science and the Institute of Sport, Exercise & Health, said: “This is the first time we’ve directly measured ovulation in this context and we found that cognitive performance was at its best during this phase, with participants reacting around 30 milliseconds faster compared to later in their cycle, during the mid-luteal phase before periods begin. At elite level, this could make the difference between sustaining a serious injury in a collision or not.

“But the really interesting finding for me is that the difference between those who were active and inactive was much greater at around 70 milliseconds, which is enough time for the brain to register a stimulus and initiate a voluntary reaction, and is therefore far more meaningful for everyday life.

“This shows the importance of incorporating some form of recreational physical activity into our lives. It doesn’t have to be that intense or competitive to make a difference – and crucially, it’s something that we can control.”

The research included 54 women aged 18-40 who were naturally menstruating (not using hormone-based contraception), who were categorised into four groups based on their athletic participation level: inactive (reported not taking part in any form of structured exercise), recreationally active (taking part in at least two hours of structured exercise a week), competing in any sport at club level, and elite (competing in any sport at national or international level)1.

The researchers tracked participants across the four key phases of the menstrual cycle. Participants completed a 10-part questionnaire to assess their mood and completed cognitive tests2 on the first day of menstruation, two days after the end of menstruation (late follicular phase), the first day ovulation was detected, and between ovulation and menstruation (mid-luteal phase).

Confirming previous findings from UCL researchers, the new study showed that reaction times were slower during the mid-luteal phase, likely due to increased levels of the female sex hormone progesterone, which is known to slow the brain down. However, this did not lead to more errors, suggesting that slower processing speeds observed during this phase do not necessarily compromise accuracy.

More errors were seen in the late follicular phase (just after the period ends). The researchers say it is not known yet why this would be the case.

Participants again reported lower energy and more symptoms during menstruation, yet these subjective experiences did not correlate with actual performance. 55% of participants believed their symptoms during menstruation were impairing their performance, but the researchers found no evidence of this – in fact, reaction time was also faster than during the mid-luteal phase.

Evelyn Watson, an author of the study from UCL Surgery and Interventional Science and the Institute of Sport, Exercise & Health, said: “It’s great to see that, while participants assumed that they were performing worse during menstruation, the findings don’t demonstrate any detriment to cognition. If anything, cognitive performance peaked during ovulation. This is a positive outcome that we hope can help develop a new narrative in female health and performance.”

Dr Ronca concluded: “Working exercise into our day doesn’t need to be difficult. Some of our previous studies have shown that 15 minutes of moderate activity is enough to boost our mood and cognitive performance, that’s equivalent to taking a brisk walk around the block or cycling to the shops.”

Reference:

Ronca, F., Watson, E., Metcalf, I. et al. Menstrual Cycle and Athletic Status Interact to Influence Symptoms, Mood, and Cognition in Females. Sports Med – Open 11, 104 (2025). https://doi.org/10.1186/s40798-025-00924-8

Researchers have developed a material that can sense tiny changes within the body, such as during an arthritis flare-up, and release drugs exactly where and when they are needed.

The squishy material can be loaded with anti-inflammatory drugs that are released in response to small changes in pH in the body. During an arthritis flare-up, a joint becomes inflamed and slightly more acidic than the surrounding tissue.

The material, developed by researchers at the University of Cambridge, has been designed to respond to this natural change in pH. As acidity increases, the material becomes softer and more jelly-like, triggering the release of drug molecules that can be encapsulated within its structure.

Since the material is designed to respond only within a narrow pH range, the team say that drugs could be released precisely where and when they are needed, potentially reducing side effects.

If used as an artificial cartilage in arthritic joints, this approach could allow for the continuous treatment of arthritis, improving the efficacy of drugs to relieve pain and fight inflammation. Arthritis affects more than 10 million people in the UK, costing the NHS an estimated £10.2 billion annually. Worldwide it is estimated to affect over 600 million people.

While extensive clinical trials are needed before the material can be used in patients, the researchers say their approach could improve outcomes for people with arthritis, and for those with other conditions including cancer. Their results are reported in the Journal of the American Chemical Society.

The material developed by the Cambridge team uses specially engineered and reversible crosslinks within a polymer network. The sensitivity of these links to changes in acidity levels gives the material highly responsive mechanical properties.

The material was developed in Professor Oren Scherman’s research group in Cambridge’s Yusuf Hamied Department of Chemistry. The group specialises in designing and building these unique materials for a range of potential applications.

“For a while now, we’ve been interested in using these materials in joints, since their properties can mimic those of cartilage,” said Scherman, who is Professor of Supramolecular and Polymer Chemistry and Director of the Melville Laboratory for Polymer Synthesis. “But to combine that with highly targeted drug delivery is a really exciting prospect.”

“These materials can ‘sense’ when something is wrong in the body and respond by delivering treatment right where it’s needed,” said first author Dr Stephen O’Neill. “This could reduce the need for repeated doses of drugs, while improving patient quality of life.”

Unlike many drug delivery systems that require external triggers such as heat or light, this one is powered by the body’s own chemistry. The researchers say this could pave the way for longer-lasting, targeted arthritis treatments that automatically respond to flare-ups, boosting effectiveness while reducing harmful side effects.

In laboratory tests, researchers loaded the material with a fluorescent dye to mimic how a real drug might behave. They found that at acidity levels typical of an arthritic joint, the material released substantially more drug cargo compared with normal, healthy pH levels.

“By tuning the chemistry of these gels, we can make them highly sensitive to the subtle shifts in acidity that occur in inflamed tissue,” said co-author Dr Jade McCune. “That means drugs are released when and where they are needed most.”

The researchers say the approach could be tailored to a range of medical conditions, by fine-tuning the chemistry of the material. “It’s a highly flexible approach, so we could in theory incorporate both fast-acting and slow-acting drugs, and have a single treatment that lasts for days, weeks or even months,” said O’Neill.

The team’s next steps will involve testing the materials in living systems to evaluate their performance and safety in a physiological environment. The team say that if successful, their approach could open the door to a new generation of responsive biomaterials capable of treating chronic diseases with greater precision.

Reference:

Stephen J.K. O’Neill,Yuen Cheong Tse,Zehuan Huang, Kinetic Locking of pH-Sensitive Complexes for Mechanically Responsive Polymer Networks, Journal of the American Chemical Society, DOI:10.1021/jacs.5c09897