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Published on: September 2, 2022
Palmitic acid-capped MIL-101-Al as a nano-adjuvant to amplify immune responses against Pseudomonas aeruginosa
Lingming Chen1,2, Shuai Liu3, Yunting Zhang4
1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, 523808 Dongguan, Guangdong, China.
Abstract:
As a highly contagious opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa) is one of the main causes of healthcare-associated infections. The drug-resistant nature of P. aeruginosa can render antibiotic treatments ineffective, leading to a high morbidity and mortality. Higher specificity and reduced toxicity are features of immunotherapy, which can generate robust immune responses and preserve long-term immunological memory to completely eradicate infections. In this study, we developed a type of P. aeruginosa vaccine based on a metal-organic framework. Specifically, MIL-101-Al nanoparticles were synthesized to encapsulate antigens derived from the bacterial lysate (BL) of PAO1, a drug-resistant P. aeruginosa, and the adjuvant unmethylated cytosine-phosphate-guanine oligonucleotide (CpG), which were then modified with palmitic acid (PAA) to obtain MIL-BC@PAA. The stability and biocompatibility were significantly increased by capping with PAA. Moreover, MIL-BC@PAA showed significantly enhanced uptake by antigen presenting cells (APCs), and promoted their maturation. Importantly, immunity studies revealed the greatly elicited antigen-specific humoral and cellular responses, and a protection rate of about 70% was observed in P. aeruginosa-challenged mice. Overall, these results demonstrate the promising potential of MIL-BC@PAA as an ideal nanovaccine for P. aeruginosa vaccination.
Insights
A novel nanovaccine, MIL-BC@PAA, effectively targets drug-resistant Pseudomonas aeruginosa. This metal-organic framework vaccine enhances immune responses and provides significant protection against infection in mice.
Area of Science:
- Biotechnology
- Immunology
- Materials Science
Background:
- Pseudomonas aeruginosa (P. aeruginosa) is a major cause of difficult-to-treat healthcare-associated infections due to its drug resistance.
- Antibiotic treatments are often ineffective against P. aeruginosa, leading to high morbidity and mortality.
- Immunotherapy offers a promising alternative with high specificity and reduced toxicity.
Purpose of the Study:
- To develop a novel nanovaccine for P. aeruginosa using a metal-organic framework.
- To enhance vaccine stability, biocompatibility, and immune cell uptake.
- To evaluate the immunogenicity and protective efficacy of the developed nanovaccine.
Main Methods:
- Synthesis of MIL-101-Al nanoparticles encapsulating P. aeruginosa antigens (bacterial lysate) and CpG adjuvant.
- Modification of nanoparticles with palmitic acid (PAA) to form MIL-BC@PAA.
- Assessment of nanoparticle stability, biocompatibility, antigen-presenting cell (APC) uptake and maturation, and immune responses in mice.
Main Results:
- MIL-BC@PAA demonstrated enhanced stability and biocompatibility.
- The nanovaccine significantly increased APC uptake and maturation.
- Robust antigen-specific humoral and cellular immune responses were elicited.
- Approximately 70% protection was observed in P. aeruginosa-challenged mice.
Conclusions:
- MIL-BC@PAA shows significant potential as an effective nanovaccine against P. aeruginosa.
- The metal-organic framework approach offers a promising strategy for developing vaccines against drug-resistant bacteria.
- Further research into this nanovaccine platform could lead to improved treatments for P. aeruginosa infections.
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