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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.”