The USC-patented shot would protect patients from hospital-acquired infections.
What
if a vaccine, given to patients just before or after arriving at the hospital,
could protect them against lethal superbugs that lurk in health care settings?
That’s
the premise behind an experimental vaccine invented by a USC-led team and
patented by the university. Researchers designed the formula to prevent serious
infections from drug-resistant pathogens. A new study shows that a single dose,
administered in mouse models, put immune cells into “Incredible Hulk” mode,
providing rapid protection against nine different bacteria and fungi species.
“It’s an early warning system. It’s like Homeland Security putting out a terror alert. ‘Everybody, keep your eyes open. Keep an eye out for suspicious packages’,” said senior author Brad Spellberg, chief medical officer at the USC-affiliated Los Angeles General Medical Center (formerly Los Angeles County+USC Medical Center).
The
study appears Wednesday in Science Translational Medicine.
The USC Stevens Center for
Innovation — the technology licensing office for USC —
successfully filed for a patent on the vaccine. The National Institute of
Allergy and Infectious Diseases, part of the National Institutes of
Health, gave startup company ExBaq LLC nearly $1 million in the form
of a small-business grant, aimed at speeding up solutions to high-priority
problems.
“The pandemic stimulated unprecedented innovation in vaccine development, where federal funding and university-industry partnerships were game changers for translating promising discoveries from academic labs for the good of all,” said Ishwar K. Puri, senior vice president of research and innovation at USC.
“We are both pleased and proud of the
critical support the USC Stevens Center provided to enable the development of
ExBaq’s experimental vaccine that protects vulnerable populations from serious
infections.”
Every
year, health care-acquired infections kill more than 90,000 people in the
United States and rack up health care costs between $28 billion and $45
billion. On any given day, about 1 in 31 hospital patients has at least one
health care-associated infection, according to the Centers for Disease Control
and Prevention.
Vaccine
aimed at infections often caused by superbugs such as MRSA
In many cases, infections are caused by so-called superbugs such as MRSA — short for methicillin-resistant Staphylococcus aureus — or Acinetobacter baumannii.
The infections spread via contaminated surfaces or
equipment such as catheters or ventilators or though person to person spread,
often from contaminated hands. Risk is highest among patients in the ICU,
resulting in surgical site infections, bloodstream infections, urinary tract
infections and ventilator-associated pneumonia.
Typical
vaccines usually prompt the body to make antibodies against a specific
pathogen. Despite the high incidence of health care-acquired infections, there
are currently no FDA-approved vaccines that prevent the most serious
antibiotic-resistant infections.
“Even
if there were such vaccines, multiple vaccines would have to be deployed
simultaneously to protect against the full slate of antibiotic-resistant
microbes that cause health care-acquired infections,” said Brian Luna, assistant professor of molecular
microbiology and immunology at the Keck School of Medicine of USC.
The
experimental vaccine takes an entirely different approach: It gooses the body’s
preexisting supply of pathogen-gobbling immune cells called macrophages, which
engulf and digest bacteria, fungi and other bad actors. These activated
fighters, found in all tissues, quickly neutralize incoming invaders which
might otherwise multiply rapidly and overwhelm the body’s defenses.
“This
is very different from developing new antibiotics,” said Jun Yan, a doctoral
student at Keck School of Medicine and the study’s first author. “This is using
our own immune system to fight against different superbugs, which is a
different approach than everybody else.”
The
vaccine is made up of just three ingredients, two of which are already used in
FDA-approved vaccines. A third component is a tiny piece from the surface of a
fungus commonly found on human skin.
MRSA
vaccine works within 24 hours
Tested
in two independent labs, the vaccine works within 24 hours and lasts for up to
28 days. In lab models, the number of pathogen-eating immune cells in the blood
increased dramatically, and survival time of invasive blood and lung infections
improved. Early data suggest that a second dose could extend the window to
prevent infection.
To
develop the vaccine, Spellberg, Luna, Yan and Travis Nielsen, who earned his
PhD in the Keck School of Medicine’s biomedical and biological sciences program
before going to medical school, formed a startup called ExBaq LLC.
ExBaq
began talking with potential larger partners who might be willing to help
develop the vaccine into clinical testing. AstraZeneca expressed interest in
learning more about the vaccine, Spellberg said, and then agreed to test it in
its own experimental infection models, confirming that it worked in those
models too.
The next step is getting guidance from the FDA on the design of a clinical trial. 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.
In addition to Yan, Luna, Spellberg and Nielsen, other
authors of the paper are Peggy Lu, Yuli Talyansky, Matt Slarve and Hernan Reza,
all of the department of molecular microbiology and immunology at the Keck
School of Medicine of USC; Boris Novakovic of University of Melbourne; Mihai
Netea of Radboud University; and Ashley Keller, Troy Warren, Antonio
DiGiandomenico and Bret Sellman, all of AstraZeneca.
The study was supported by grants from the National
Institute of Allergy and Infectious Diseases at the National Institutes of
Health (R01 AI130060, R42 STTR AI106375, R01 AI139052 and 5P30 AI028697).
