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Academic Journal
Live attenuated hfq-deleted Acinetobacter baumannii vaccine provides protection against systemic infection.
Bakht P, Hussain A, Pandey S, Pathania R
Vaccine [Vaccine] 2025 Jun 20; Vol. 59, pp. 127298. Date of Electronic Publication: 2025 May 23.
2025
Sparad:
Titel | Live attenuated hfq-deleted Acinetobacter baumannii vaccine provides protection against systemic infection. |
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Författarna | Bakht P, Hussain A, Pandey S, Pathania R |
Källa |
Vaccine [Vaccine] 2025 Jun 20; Vol. 59, pp. 127298. Date of Electronic Publication: 2025 May 23.
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Abstrakt |
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ranjana Pathania reports financial support was provided by Scheme for Transformational and Advanced Research in Sciences, Ministry of Education, Government of India with grant code No. MoE/STARS-1/614 (Letter No. STARS/APR2019/BS/614/FS). Ranjana Pathania has patent "A composition for protection against infections by multidrug-resistant Acinetobacter baumannii and its method of preparation" pending at the Indian Patent Office (App. No. 202411072961). Perwez Bakht, Arsalan Hussain, Shivam Pandey has patent "A composition for protection against infections by multidrug-resistant Acinetobacter baumannii and its method of preparation" pending at the Indian Patent Office (App. No. 202411072961). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen with high mortality rates, necessitating alternative preventive strategies. The RNA chaperone Hfq plays a key role in bacterial virulence, and its deletion attenuates pathogenicity. In this study, we evaluated an hfq deletion mutant (Δhfq) of A. baumannii ATCC 17978 as a live-attenuated vaccine candidate. Mice vaccinated intraperitoneally with 2.3 × 10 7 CFU of Δhfq, followed by a booster on day 28, exhibited 90 % survival after an intraperitoneal lethal challenge with MDR A. baumannii AB5075, whereas all unvaccinated controls succumbed. Vaccinated mice showed a significant reduction in bacterial burden in key organs (p < 0.001), sustained IgG levels, and an enhanced cytokine response with early IFN-γ and TNF-α activation, followed by a controlled IL-10 response. Serum pentraxin-3 (PTX3) levels were significantly lower in vaccinated mice post-challenge, correlating with reduced systemic inflammation and sepsis risk. Histopathological analysis revealed intact organ architecture in vaccinated mice, while unvaccinated mice displayed severe pathology. Functional immunogenicity assays demonstrated that serum from vaccinated mice enhanced neutrophil-mediated bacterial killing, and passive transfer of heat-inactivated serum conferred complete protection, confirming antibody-mediated immunity independent of complement activation. These findings highlight Δhfq as a promising live-attenuated vaccine that induces strong humoral and cellular immunity, preventing bacterial dissemination and lethal infection. Further studies are needed to elucidate its protective mechanisms and clinical potential. (Copyright © 2025 Elsevier Ltd. All rights reserved.) |
Språk |
English
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Tidskrift info |
Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE
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MeSH-termer |
Acinetobacter baumannii*/immunology , Acinetobacter baumannii*/genetics , Acinetobacter baumannii*/pathogenicity , Acinetobacter Infections*/prevention & control , Acinetobacter Infections*/immunology , Bacterial Vaccines*/immunology , Bacterial Vaccines*/administration & dosage , Host Factor 1 Protein*/genetics , Sepsis*/prevention & control, Animals ; Vaccines, Attenuated/immunology ; Vaccines, Attenuated/administration & dosage ; Mice ; Female ; Antibodies, Bacterial/blood ; Cytokines ; Immunoglobulin G/blood ; Mice, Inbred BALB C ; Immunization, Passive ; Immunogenicity, Vaccine ; Neutrophils/immunology ; Disease Models, Animal
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Update Code |
20250605
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