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Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
Developing adjuvant vaccines to combat rising multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections is a promising and cost-effective approach. The aim of this analysis was to construct a pDNA-CPG C274-adjuvant nano-vaccine and investigate its immunogenicity and protection in B...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008545/ https://www.ncbi.nlm.nih.gov/pubmed/36905472 http://dx.doi.org/10.1186/s13568-023-01531-0 |
Sumario: | Developing adjuvant vaccines to combat rising multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections is a promising and cost-effective approach. The aim of this analysis was to construct a pDNA-CPG C274-adjuvant nano-vaccine and investigate its immunogenicity and protection in BALB/c mice. The CPG ODN C274 adjuvant was chemically synthesized and cloned into pcDNA3.1( +), and the cloning was verified using PCR and BamHI/EcoRV restriction enzyme digestion. Then, utilizing a complex coacervation approach, pDNA-CPG C274 was encapsulated by chitosan (CS) nanoparticles (NPs). TEM and DLS are used to explore the properties of the pDNA/CSNP complex. TLR-9 pathway activation was investigated in human HEK-293 and RAW 264.7 mouse cells. The vaccine's immunogenicity and immune-protective effectiveness were investigated in BALB/c mice. The pDNA-CPG C274/CSNPs were small (mean size 79.21 ± 0.23 nm), positively charged (+ 38.87 mV), and appeared to be spherical. A continuous slow release pattern was achieved. TLR-9 activation was greatest in the mouse model with CpG ODN (C274) at concentrations of 5 and 10 μg/ml with 56% and 55%, respectively (**P < 0.01). However, in HEK-293 human cells, by increasing the concentration of CpG ODN (C274) from 1 to 50 μg/ml, the activation rate of TLR-9 also increased, so that the highest activation rate (81%) was obtained at the concentration of 50 μg/ml (***P < 0.001). pDNA-CPG C274/CSNPs immunized BALB/c mice produced increased amounts of total-IgG, as well as IFN-γ and IL-1B in serum samples, compared to non-encapsulated pDNA-CPG C274. Furthermore, liver and lung injuries, as well as bacterial loads in the liver, lung, and blood, were reduced, and BALB/c mice immunized with pDNA-CPG C274/CSNPs showed potent protection (50–75%) against acute fatal Intraperitoneal A. baumannii challenge. pDNA-CPG C274/CSNPs evoked total-IgG antibodies, Th1 cellular immunity, and the TLR-9 pathway, as well as protection against an acute fatal A. baumannii challenge. Our findings suggest that this nano-vaccine is a promising approach for avoiding A. baumannii infection when used as a powerful adjuvant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13568-023-01531-0. |
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