Thu. Jan 20th, 2022

New encapsulation technology for whole cell vaccines stimulates increased immunogenicity againstEscherichia coliin a mouse model that shapes the future of urine treaty infection vaccines (UTI).

Recurrent UTIs may soon be a thing of the past as researchers develop a new encapsulation technology for whole-cell vaccines. Co-senior writers Nicole De Nisco and Jeremiah Gassensmed(both University of Texas; TX, USA) collaborated on an interdisciplinary project that developed a whole cell vaccine for UTI. The group demonstrated how their whole-cell bacteria encapsulated in a metal-organic framework (MOF) increase antibody production in mice and provide a promising alternative to antibiotics and inactivated standard vaccines.

UTIs are a major burden on the healthcare system, especially in an era of antibiotic resistance.The American Urological Association estimates that 150 million UTIs occur globally each year, accounting for $ 6 billion in medical expenses. Recurrent urinary tract infections pose a health threat to many, especially in postmenopausal women, which, unless treated successfully, can result in sepsis.

“Every subsequent infection becomes more difficult to treat,” De Nisco explained. “Even if you remove the bacteria from the bladder, populations continue elsewhere and usually become resistant to the antibiotic used. When patients accumulate antibiotic resistance, they will eventually run out of opportunities.”

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Whole cell vaccines are preferable to traditional single antigen vaccines in potentially fatal infections such as UTIs due to the size difference between bacteria and viruses; the bacteria simply have too many antigens for researchers to choose from. Creation of a whole cell vaccine enables the presentation of all the pathogenic antigens to trigger a more efficient immune response.

However, the whole cell approach also has its shortcomings. “Vaccines that use dead whole-cell bacteria have not been successful because the cells typically do not last long enough in the body to produce long-term, lasting immune responses,” Gassensmith elaborated. To tackle this problem, Gassensmith’s team developed MOFs that encapsulate and immobilize individual bacteria in a crystalline polymer matrix capable of withstanding high temperatures, moisture, and organic solvents. “It allows an intact, dead pathogen to exist in tissues longer, as if it were an infection, to trigger a full-scale immune system response,” Gassensmith explained.

The study showed that the MOF whole cell vaccine was effective against uropathogensE coli,which causes approximately 80% of all socially acquired UTIs. “When we challenged these mice with a lethal injection of bacteria after they were vaccinated, almost all of our animals survived, which is a much better performance than with traditional vaccine methods,” Gassensmith said. “This result was repeated several times and we are quite impressed with how reliable it is.”

The authors hope to test the antigen depot against other bacterial infections such as endocarditis and tuberculosis. Ultimately, this technology has the potential to help millions of patients if it can be widely used for bacterial infections, De Nisco argued.

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