Vaccine Shown to Protect Against Multiple Hospital Pathogens

Scanning electron micrograph of methicillin-resistant Staphylococcus aureus, or MRSA, in brown spheres, surrounded by cellular debris. (NIAID, NIH)

5 Oct. 2023. Research with lab mice shows an experimental vaccine stimulates the body’s basic immune system to protect against a range of pathogens associated with hospital infections. A team from University of Southern California, Los Angeles General Medical Center, and a spin-off company ExBaq LLC published their findings in yesterday’s issue of the journal Science Translational Medicine (paid registration required).

According to Centers for Disease Control and Prevention, as of 2018, one in 31 hospital patients will acquire at least one infection as a result of a hospital stay. Since that time, due in large part to more extended hospital visits from the Covid-19 pandemic, some types of health care-acquired infections increased, particularly ventilator-associated infections. During that same time, Clostridioides difficile or C. diff infections decreased, attributed to better hand-washing practices. Some of the continuing so-called superbugs, such as methicillin-resistant Staphylococcus aureus or MRSA, spread on contaminated surfaces, such as catheters, with patients in intensive care units often at higher risk.

The study team is seeking better tools for health care facilities to fight-off infections in their most vulnerable patients. Even with the infection problem increasing, vaccines to prevent infections are designed to address single pathogens, not the collection of bacteria and fungi that can infect hospitalized patients. As a result, the researchers use a strategy to stimulate the innate immune system, the body’s fact-acting first line of defense against infections that responds to suspected invaders.

To invoke the innate immune system, the team designed a vaccine to stimulate a response from macrophages, white blood cells in the immune system that first appear as cells called monocytes, precursors to macrophages. Monocytes enter the infected areas then transform into large macrophage cells to fight-off the invading pathogen. In addition, when macrophages digest target pathogens, they express antigens on their surface that attract more infection-fighting cells.

No proteins in the vaccine

“This is very different from developing new antibiotics,” says USC doctoral candidate and lead author Jan Yun in a university statement. “This is using our own immune system to fight against different superbugs, which is a different approach than everybody else.”

To generate a macrophage response, the researchers designed a vaccine with aluminum hydroxide, monophosphoryl lipid A, and mannan. Aluminum hydroxide is an adjuvant that enhances immunity, while monophosphoryl lipid A stimulates the transcription factor NF-KB, a key regulator of innate and adaptive immunity. Both aluminum hydroxide and monophosphoryl lipid A are found in vaccines already approved by FDA. Mannan is a naturally occurring fungal compound that can also stimulate monocyte and macrophage responses. None of the ingredients are proteins.

The researchers tested the vaccine on lab mice induced with blood or lung infections from several leading hospital-acquired bacteria: MRSA, vancomycin-resistant Enterococcus faecalis, Escherichia coli or E. coli, and resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Mice given the vaccine, says the team, show reduced bacterial burden and longer survival times. In addition, when given as preventive measure, the vaccine protects lab mice against infections from the fungi Rhizopus delemar and Candida albicans. The researchers report the vaccine takes effect in mice within 24 hours and a single dose protects for up to 28 days.

Yan, with co-authors Travis Nielsen, Brian Luna, and Brad Spelberg founded the company ExBaq LLC in 2017 to further develop  and commercialize their discoveries. The company licenses its technology from USC, and in 2020 received a Small Business Technology Transfer award from National Institute of Allergy and Infectious Diseases, part of NIH, to advance the vaccine through pre-clinical stages, with Spelberg — chief medical officer at L.A. General — as lead investigator.

In an ExBaq statement released through Globe NewsWire, Spelberg says the next task is to prepare for FDA clinical trial clearance. “The next step is getting guidance from the FDA on the requirements to complete preclinical studies and submit an Investigational New Drug Application in 2024,” says Spelberg. “The first such trial would be done in healthy volunteers to find the right dose of vaccine that is safe and triggers the same kind of immune response in people as seen in the mice.”

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