鲍曼不动杆菌疫苗研究新进展
New Progress of Research on Vaccines against Acinetobacter baumannii
DOI: 10.12677/acm.2025.1551367, PDF,   
作者: 薛倩蓉*:西安医学院研究生工作部,陕西 西安;空军军医大学唐都医院呼吸与危重症医学科,陕西 西安;潘 蕾#:空军军医大学唐都医院呼吸与危重症医学科,陕西 西安
关键词: 鲍曼不动杆菌感染疫苗灭活全菌体疫苗外膜囊泡疫苗重组蛋白亚单位疫苗荚膜多糖疫苗DNA疫苗佐剂纳米颗粒Acinetobacter baumannii (AB) Infection Vaccine Inactived Whole Cell Vaccine Out Membrane Vesicles Vaccine Recombinant Protein Subunit Vaccine Capsular Polysaccharide Candidate Vaccine DNA Vaccine Adjuvant Nanoparticle
摘要: 鲍曼不动杆菌是引起医院获得性感染的重要机会致病菌之一,随着多重耐药及广泛耐药菌的不断出现,其临床治疗面临严峻挑战。近年来,国内外学者对鲍曼不动杆菌疫苗的研制进行了不少探索,为其免疫治疗提供了新的思路。本文通过总结鲍曼不动杆菌灭活全菌体疫苗、外膜囊泡疫苗、重组蛋白亚单位疫苗、荚膜多糖疫苗、DNA疫苗及疫苗佐剂的最新研制成果,对鲍曼不动杆菌抗菌疫苗现状做阐述、分析及前景展望。
Abstract: Acinetobacter baumannii (AB) is one of the main opportunistic pathogens causing nosocomial infection. With the rapid emergence of multi-drug and pan-drug resistant strains, its clinical treatment encounters significant challenges. Numerous scholars try to explore and develop vaccine in control of AB infection, including inactived whole cell vaccine, out membrane vesicles vaccine, recombinant protein subunit vaccine, capsular polysaccharide candidate vaccine, DNA vaccine and adjuvant. In this paper, the current situation of various vaccines for AB is reviewed, so as to elaborate on the prospects of their development.
文章引用:薛倩蓉, 潘蕾. 鲍曼不动杆菌疫苗研究新进展[J]. 临床医学进展, 2025, 15(5): 267-275. https://doi.org/10.12677/acm.2025.1551367

参考文献

[1] Ayoub Moubareck, C. and Hammoudi Halat, D. (2020) Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen. Antibiotics, 9, Article 119. [Google Scholar] [CrossRef] [PubMed]
[2] Antimicrobial Resistance Collaborators (2022) Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. Lancet, 399, 629-655.
[3] Rosini, R., Nicchi, S., Pizza, M. and Rappuoli, R. (2020) Vaccines Against Antimicrobial Resistance. Frontiers in Immunology, 11, Article 1048. [Google Scholar] [CrossRef] [PubMed]
[4] Peana, M., Gumienna-Kontecka, E., Piras, F., Ostrowska, M., Piasta, K., Krzywoszynska, K., et al. (2020) Exploring the Specificity of Rationally Designed Peptides Reconstituted from the Cell-Free Extract of Deinococcus radiodurans toward Mn(II) and Cu(II). Inorganic Chemistry, 59, 4661-4684. [Google Scholar] [CrossRef] [PubMed]
[5] Dollery, S.J., Zurawski, D.V., Gaidamakova, E.K., Matrosova, V.Y., Tobin, J.K., Wiggins, T.J., et al. (2021) Radiation-inactivated Acinetobacter baumannii Vaccine Candidates. Vaccines, 9, Article 96. [Google Scholar] [CrossRef] [PubMed]
[6] Dollery, S.J., Zurawski, D.V., Bushnell, R.V., Tobin, J.K., Wiggins, T.J., MacLeod, D.A., et al. (2022) Whole-Cell Vaccine Candidates Induce a Protective Response against Virulent Acinetobacter baumannii. Frontiers in Immunology, 13, Article 941010. [Google Scholar] [CrossRef] [PubMed]
[7] Khan, M.A., Allemailem, K.S., Maswadeh, H. and Younus, H. (2022) Safety and Prophylactic Efficacy of Liposome-Based Vaccine against the Drug-Resistant Acinetobacter baumannii in Mice. Pharmaceutics, 14, Article 1357. [Google Scholar] [CrossRef] [PubMed]
[8] Khan, M.A., Allemailem, K.S., Maswadeh, H. and Younus, H. (2022) Glycosphingolipids (GSLs) from Sphingomonas paucimobilis Increase the Efficacy of Liposome-Based Nanovaccine against Acinetobacter baumannii-Associated Pneumonia in Immunocompetent and Immunocompromised Mice. Molecules, 27, Article 7790. [Google Scholar] [CrossRef] [PubMed]
[9] Cai, W., Kesavan, D.K., Cheng, J., Vasudevan, A., Wang, H., Wan, J., et al. (2019) Vesicle-Mediated Dendritic Cell Activation in Acinetobacter baumannii Clinical Isolate, Which Contributes to Th2 Response. Journal of Immunology Research, 2019, Article ID: 2835256. [Google Scholar] [CrossRef] [PubMed]
[10] Li, S., Chen, D., Ji, L., Sun, S., Jin, Z., Jin, Z., et al. (2020) Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy. Frontiers in Immunology, 11, Article 1069. [Google Scholar] [CrossRef] [PubMed]
[11] Higham, S.L., Baker, S., Flight, K.E., Krishna, A., Kellam, P., Reece, S.T., et al. (2023) Intranasal Immunization with Outer Membrane Vesicles (OMV) Protects against Airway Colonization and Systemic Infection with Acinetobacter baumannii. Journal of Infection, 86, 563-573. [Google Scholar] [CrossRef] [PubMed]
[12] Lung, P., Yang, J. and Li, Q. (2020) Nanoparticle Formulated Vaccines: Opportunities and Challenges. Nanoscale, 12, 5746-5763. [Google Scholar] [CrossRef] [PubMed]
[13] Bjanes, E., Zhou, J., Qayum, T., Krishnan, N., Zurich, R.H., Menon, N.D., et al. (2022) Outer Membrane Vesicle‐Coated Nanoparticle Vaccine Protects against Acinetobacter baumannii Pneumonia and Sepsis. Advanced NanoBiomed Research, 3, Article ID: 2200130. [Google Scholar] [CrossRef] [PubMed]
[14] Cecil, J.D., Sirisaengtaksin, N., O’Brien-Simpson, N.M. and Krachler, A.M. (2019) Outer Membrane Vesicle-Host Cell Interactions. Microbiology Spectrum, 7. [Google Scholar] [CrossRef] [PubMed]
[15] Pulido, M.R., García-Quintanilla, M., Pachón, J. and McConnell, M.J. (2020) A Lipopolysaccharide-Free Outer Membrane Vesicle Vaccine Protects against Acinetobacter baumannii Infection. Vaccine, 38, 719-724. [Google Scholar] [CrossRef] [PubMed]
[16] Yang, N., Jin, X., Zhu, C., Gao, F., Weng, Z., Du, X., et al. (2023) Subunit Vaccines for Acinetobacter baumannii. Frontiers in Immunology, 13, Article 1088130. [Google Scholar] [CrossRef] [PubMed]
[17] Gellings, P.S., Wilkins, A.A. and Morici, L.A. (2020) Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine. Pathogens, 9, Article 1066. [Google Scholar] [CrossRef] [PubMed]
[18] Nie, D., Hu, Y., Chen, Z., Li, M., Hou, Z., Luo, X., et al. (2020) Outer Membrane Protein a (OmpA) as a Potential Therapeutic Target for Acinetobacter baumannii Infection. Journal of Biomedical Science, 27, Article No. 26. [Google Scholar] [CrossRef] [PubMed]
[19] Zhang, X., Yang, T., Cao, J., Sun, J., Dai, W. and Zhang, L. (2016) Mucosal Immunization with Purified OmpA Elicited Protective Immunity against Infections Caused by Multidrug-Resistant Acinetobacter baumannii. Microbial Pathogenesis, 96, 20-25. [Google Scholar] [CrossRef] [PubMed]
[20] Viale, A.M. and Evans, B.A. (2020) Microevolution in the Major Outer Membrane Protein OmpA of Acinetobacter baumannii. Microbial Genomics, 6, e000381. [Google Scholar] [CrossRef] [PubMed]
[21] Ramezanalizadeh, F., Rasooli, I. and Owlia, P. (2021) Protective Response against Acinetobacter baumannii with Ferric Iron Receptors HemTR-BauA in a Murine Sepsis Model. Future Microbiology, 16, 159-173. [Google Scholar] [CrossRef] [PubMed]
[22] Akbari, Z., Rasooli, I., Ghaini, M.H., Chaudhuri, S., Farshchi Andisi, V., Jahangiri, A., et al. (2022) BauA and Omp34 Surface Loops Trigger Protective Antibodies against Acinetobacter baumannii in a Murine Sepsis Model. International Immunopharmacology, 108, Article ID: 108731. [Google Scholar] [CrossRef] [PubMed]
[23] Tamehri, M., Rasooli, I., Pishgahi, M., Jahangiri, A., Ramezanalizadeh, F. and Banisaeed Langroodi, S.R. (2022) Combination of BauA and OmpA Elicit Immunoprotection against Acinetobacter baumannii in a Murine Sepsis Model. Microbial Pathogenesis, 173, Article ID: 105874. [Google Scholar] [CrossRef] [PubMed]
[24] Smani, Y., Fàbrega, A., Roca, I., Sánchez-Encinales, V., Vila, J. and Pachón, J. (2014) Role of OmpA in the Multidrug Resistance Phenotype of Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy, 58, 1806-1808. [Google Scholar] [CrossRef] [PubMed]
[25] Raoufi, Z., Abdollahi, S. and Armand, R. (2022) DcaP Porin and Its Epitope-Based Subunit Promise Effective Vaccines against Acinetobacter baumannii; In-Silico and In-Vivo Approaches. Microbial Pathogenesis, 162, Article ID: 105346. [Google Scholar] [CrossRef] [PubMed]
[26] Fereshteh, S., Ajdary, S., Sepehr, A., Bolourchi, N., Barzi, S.M., Haririzadeh Jouriani, F., et al. (2023) Immunization with Recombinant DcaP-Like Protein and AbOmpA Revealed Protections against Sepsis Infection of Multi-Drug Resistant Acinetobacter baumannii ST2pas in a C57BL/6 Mouse Model. Microbial Pathogenesis, 174, Article ID: 105882. [Google Scholar] [CrossRef] [PubMed]
[27] Rumbo, C., Tomás, M., Fernández Moreira, E., Soares, N.C., Carvajal, M., Santillana, E., et al. (2014) The Acinetobacter baumannii Omp33-36 Porin Is a Virulence Factor That Induces Apoptosis and Modulates Autophagy in Human Cells. Infection and Immunity, 82, 4666-4680. [Google Scholar] [CrossRef] [PubMed]
[28] Naghipour Erami, A., Rasooli, I., Jahangiri, A. and Darvish Alipour Astaneh, S. (2021) Anti-Omp34 Antibodies Protect against Acinetobacter baumannii in a Murine Sepsis Model. Microbial Pathogenesis, 161, Article ID: 105291. [Google Scholar] [CrossRef] [PubMed]
[29] Golestani, F., Malekan, M., Rasooli, I., Jahangiri, A., Ramezanalizadeh, F., Chaudhuri, S., et al. (2022) Immunogenicity of Loop 3 of Omp34 from A. Baumannii in Loopless C-Lobe of TbpB of N. Meningitidis. International Immunopharmacology, 110, Article ID: 109013. [Google Scholar] [CrossRef] [PubMed]
[30] Mirali, M., Jahangiri, A., Jalali Nadoushan, M. and Rasooli, I. (2023) A Two-Protein Cocktail Elicits a Protective Immune Response against Acinetobacter baumannii in a Murine Infection Model. Microbial Pathogenesis, 182, Article ID: 106262. [Google Scholar] [CrossRef] [PubMed]
[31] Guo, S.J., Ren, S., and Xie, Y.E. (2018) Evaluation of the Protective Efficacy of a Fused OmpK/Omp22 Protein Vac-cine Candidate against Acinetobacter baumannii Infection in Mice. Biomedical and Environmental Sciences: BES, 31, 155-158.
[32] Yang, A., Yang, H., Guo, S. and Xie, Y. (2019) MF59 Adjuvant Enhances the Immunogenicity and Protective Immunity of the OmpK/omp22 Fusion Protein from Acineterbacter baumannii through Intratracheal Inoculation in Mice. Scandinavian Journal of Immunology, 90, e12769. [Google Scholar] [CrossRef] [PubMed]
[33] Du, X., Xue, J., Jiang, M., Lin, S., Huang, Y., Deng, K., et al. (2021) A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine against Acinetobacter baumannii Infection. International Journal of Nanomedicine, 16, 1819-1836. [Google Scholar] [CrossRef] [PubMed]
[34] Sabzi, S., Habibi, M., Badmasti, F., Shahbazi, S., Asadi Karam, M.R. and Farokhi, M. (2024) Polydopamine-Based Nano Adjuvant as a Promising Vaccine Carrier Induces Significant Immune Responses against Acinetobacter baumannii-Associated Pneumonia. International Journal of Pharmaceutics, 654, Article ID: 123961. [Google Scholar] [CrossRef] [PubMed]
[35] Singh, R., Capalash, N. and Sharma, P. (2017) Immunoprotective Potential of Bama, the Outer Membrane Protein Assembly Factor, against MDR Acinetobacter baumannii. Scientific Reports, 7, Article No. 12411. [Google Scholar] [CrossRef] [PubMed]
[36] Vieira de Araujo, A.E., Conde, L.V., da Silva Junior, H.C., de Almeida Machado, L., Lara, F.A., Chapeaurouge, A., et al. (2021) Cross-Reactivity and Immunotherapeutic Potential of Bama Recombinant Protein from Acinetobacter baumannii. Microbes and Infection, 23, Article ID: 104801. [Google Scholar] [CrossRef] [PubMed]
[37] Heidarinia, H., Tajbakhsh, E., Rostamian, M. and Momtaz, H. (2023) Epitope Mapping of Acinetobacter baumannii Outer Membrane Protein W (OmpW) and Laboratory Study of an OmpW-Derivative Peptide. Heliyon, 9, e18614. [Google Scholar] [CrossRef] [PubMed]
[38] Abdollahi, S. and Raoufi, Z. (2023) A Novel Vaccine Candidate against A. baumannii Based on a New OmpW Family Protein (OmpW2); Structural Characterization, Antigenicity and Epitope Investigation, and In-Vivo Analysis. Microbial Pathogenesis, 183, Article ID: 106317. [Google Scholar] [CrossRef] [PubMed]
[39] Sianturi, J., Priegue, P., Hu, J., Yin, J. and Seeberger, P.H. (2022) Semi‐Synthetic Glycoconjugate Vaccine Lead against Acinetobacter baumannii 17978. Angewandte Chemie International Edition, 61, e202209556. [Google Scholar] [CrossRef] [PubMed]
[40] Yang, F., Lou, T., Kuo, S., Wu, W., Chern, J., Lee, Y., et al. (2017) A Medically Relevant Capsular Polysaccharide in Acinetobacter baumannii Is a Potential Vaccine Candidate. Vaccine, 35, 1440-1447. [Google Scholar] [CrossRef] [PubMed]
[41] Rudenko, N., Karatovskaya, A., Zamyatina, A., Shepelyakovskaya, A., Semushina, S., Brovko, F., et al. (2022) Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins. Microbiology Spectrum, 10, e0167422. [Google Scholar] [CrossRef] [PubMed]
[42] Karatovskaya, A., Rudenko, N., Zamyatina, A., Zvonarev, A., Oleinikov, V., Shpirt, A., et al. (2023) Protective Capacity of Monoclonal Antibodies against Acinetobacter baumannii K9 Capsular Polysaccharide. Microbiology Spectrum, 11, e04141-22. [Google Scholar] [CrossRef] [PubMed]
[43] Li, L. and Petrovsky, N. (2015) Molecular Mechanisms for Enhanced DNA Vaccine Immunogenicity. Expert Review of Vaccines, 15, 313-329. [Google Scholar] [CrossRef] [PubMed]
[44] Ansari, H., Tahmasebi-Birgani, M., Bijanzadeh, M., Doosti, A. and Kargar, M. (2019) Study of the Immunogenicity of Outer Membrane Protein A (ompA) Gene from Acinetobacter baumannii as DNA Vaccine Candidate in Vivo. Iranian Journal of Basic Medical Sciences, 22, 669-675.
[45] Song, J.H., Lee, W.C., Park, J.S., Kim, S.I., Lee, J.C., Cheong, C., et al. (2012) Cloning, Purification and Preliminary X-Ray Crystallographic Analysis of the OmpA-Like Domain of Peptidoglycan-Associated Lipoprotein from Acinetobacter baumannii. Acta Crystallographica Section F Structural Biology and Crystallization Communications, 68, 1351-1353. [Google Scholar] [CrossRef] [PubMed]
[46] Lei, L., Yang, F., Zou, J., Jing, H., Zhang, J., Xu, W., et al. (2019) DNA Vaccine Encoding OmpA and Pal from Acinetobacter baumannii Efficiently Protects Mice against Pulmonary Infection. Molecular Biology Reports, 46, 5397-5408. [Google Scholar] [CrossRef] [PubMed]
[47] Pati, R., Shevtsov, M. and Sonawane, A. (2018) Nanoparticle Vaccines against Infectious Diseases. Frontiers in Immunology, 9, Article 2224. [Google Scholar] [CrossRef] [PubMed]
[48] Hosseinnezhad-Lazarjani, E., Doosti, A. and Sharifzadeh, A. (2023) Novel CsuC-DNA Nanovaccine Based on Chitosan Candidate Vaccine against Infection with Acinetobacter baumannii. Vaccine, 41, 2170-2183. [Google Scholar] [CrossRef] [PubMed]
[49] Mat Rahim, N., Lee, H., Strych, U. and AbuBakar, S. (2021) Facing the Challenges of Multidrug-Resistant Acinetobacter baumannii: Progress and Prospects in the Vaccine Development. Human Vaccines & Immunotherapeutics, 17, 3784-3794. [Google Scholar] [CrossRef] [PubMed]
[50] Lau, Y.T. and Tan, H.S. (2023) Acinetobacter baumannii Subunit Vaccines: Recent Progress and Challenges. Critical Reviews in Microbiology, 50, 434-449.
[51] Mba, I.E., Sharndama, H.C., Anyaegbunam, Z.K.G., Anekpo, C.C., Amadi, B.C., Morumda, D., et al. (2023) Vaccine Development for Bacterial Pathogens: Advances, Challenges and Prospects. Tropical Medicine & International Health, 28, 275-299. [Google Scholar] [CrossRef] [PubMed]
[52] Ud-Din, M., Albutti, A., Ullah, A., Ismail, S., Ahmad, S., Naz, A., et al. (2022) Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii. International Journal of Environmental Research and Public Health, 19, Article 5568. [Google Scholar] [CrossRef] [PubMed]