Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice
Abstract Burkholderia cenocepacia causes life-threatening infections in immunocompromised patients. Treatment is challenging due to intrinsic antibiotic multiresistance, so vaccination provides an alternative approach. We aimed to identify vaccine candidates using reverse vaccinology and evaluate th...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01074-4 |
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| author | Wesam E. Gawad Yosra I. Nagy Tamer M. Samir Ahmed Mohamed Ibrahim Mansour Omneya M. Helmy |
| author_facet | Wesam E. Gawad Yosra I. Nagy Tamer M. Samir Ahmed Mohamed Ibrahim Mansour Omneya M. Helmy |
| author_sort | Wesam E. Gawad |
| collection | DOAJ |
| description | Abstract Burkholderia cenocepacia causes life-threatening infections in immunocompromised patients. Treatment is challenging due to intrinsic antibiotic multiresistance, so vaccination provides an alternative approach. We aimed to identify vaccine candidates using reverse vaccinology and evaluate their efficacy as protein-loaded chitosan: pectin nanoparticles (C:P NPs) in a vaccine model. Applying strict subtractive channels, three proteins were shortlisted: WP_006481710.1 (LY), WP_012493605.1 (KT), and WP_006492970.1 (BD). Proteins were cloned, purified as His-tagged proteins, and loaded onto C:P NPs. Vaccinated mice had significantly higher systemic IgG and mucosal IgA antibody responses and induced IL-6 and IL-17A. 6x-His-LY-CS:P NPs and 6x-His-KT-CS:P NPs vaccines induced TNF-α. Vaccines conferred significant protection against B. cenocepacia intranasal infections. In conclusion, cyclic-di-AMP phosphodiesterase (WP_012493605.1) is a promising vaccine candidate that elicited IgG and IgA antibodies, Th1, Th2, and Th17 cellular immunity in BALB/c mice and protected against B. cenocepacia infection. This provides hope for saving lives of people at high risk of infection. |
| format | Article |
| id | doaj-art-66c6057cdd454329993933958f4c5e94 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-66c6057cdd454329993933958f4c5e942025-02-02T12:07:33ZengNature Portfolionpj Vaccines2059-01052025-02-0110111610.1038/s41541-025-01074-4Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in miceWesam E. Gawad0Yosra I. Nagy1Tamer M. Samir2Ahmed Mohamed Ibrahim Mansour3Omneya M. Helmy4Department of Microbiology and Immunology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and TechnologyDepartment of Microbiology and Immunology, Faculty of Pharmacy, Cairo UniversityDepartment of Microbiology and Immunology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and TechnologyDepartment of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Cairo UniversityAbstract Burkholderia cenocepacia causes life-threatening infections in immunocompromised patients. Treatment is challenging due to intrinsic antibiotic multiresistance, so vaccination provides an alternative approach. We aimed to identify vaccine candidates using reverse vaccinology and evaluate their efficacy as protein-loaded chitosan: pectin nanoparticles (C:P NPs) in a vaccine model. Applying strict subtractive channels, three proteins were shortlisted: WP_006481710.1 (LY), WP_012493605.1 (KT), and WP_006492970.1 (BD). Proteins were cloned, purified as His-tagged proteins, and loaded onto C:P NPs. Vaccinated mice had significantly higher systemic IgG and mucosal IgA antibody responses and induced IL-6 and IL-17A. 6x-His-LY-CS:P NPs and 6x-His-KT-CS:P NPs vaccines induced TNF-α. Vaccines conferred significant protection against B. cenocepacia intranasal infections. In conclusion, cyclic-di-AMP phosphodiesterase (WP_012493605.1) is a promising vaccine candidate that elicited IgG and IgA antibodies, Th1, Th2, and Th17 cellular immunity in BALB/c mice and protected against B. cenocepacia infection. This provides hope for saving lives of people at high risk of infection.https://doi.org/10.1038/s41541-025-01074-4 |
| spellingShingle | Wesam E. Gawad Yosra I. Nagy Tamer M. Samir Ahmed Mohamed Ibrahim Mansour Omneya M. Helmy Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice npj Vaccines |
| title | Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice |
| title_full | Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice |
| title_fullStr | Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice |
| title_full_unstemmed | Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice |
| title_short | Cyclic di AMP phosphodiesterase nanovaccine elicits protective immunity against Burkholderia cenocepacia infection in mice |
| title_sort | cyclic di amp phosphodiesterase nanovaccine elicits protective immunity against burkholderia cenocepacia infection in mice |
| url | https://doi.org/10.1038/s41541-025-01074-4 |
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