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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...

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Autores principales: Piri-Gharaghie, Tohid, Doosti, Abbas, Mirzaei, Seyed Abbas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
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
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author Piri-Gharaghie, Tohid
Doosti, Abbas
Mirzaei, Seyed Abbas
author_facet Piri-Gharaghie, Tohid
Doosti, Abbas
Mirzaei, Seyed Abbas
author_sort Piri-Gharaghie, Tohid
collection PubMed
description 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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spelling pubmed-100085452023-03-13 Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii Piri-Gharaghie, Tohid Doosti, Abbas Mirzaei, Seyed Abbas AMB Express Original Article 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. Springer Berlin Heidelberg 2023-03-11 /pmc/articles/PMC10008545/ /pubmed/36905472 http://dx.doi.org/10.1186/s13568-023-01531-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Piri-Gharaghie, Tohid
Doosti, Abbas
Mirzaei, Seyed Abbas
Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
title Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
title_full Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
title_fullStr Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
title_full_unstemmed Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
title_short Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
title_sort novel adjuvant nano-vaccine induced immune response against acinetobacter baumannii
topic Original Article
url 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
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