International Journal of Nanomedicine (Mar 2021)

A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine Against Acinetobacter baumannii Infection

  • Du X,
  • Xue J,
  • Jiang M,
  • Lin S,
  • Huang Y,
  • Deng K,
  • Shu L,
  • Xu H,
  • Li Z,
  • Yao J,
  • Chen S,
  • Shen Z,
  • Feng G

Journal volume & issue
Vol. Volume 16
pp. 1819 – 1836

Abstract

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Xingran Du,1,* Jianpeng Xue,2,* Mingzi Jiang,3 Shaoqing Lin,4 Yuzhen Huang,4 Kaili Deng,5 Lei Shu,5 Hanmei Xu,2 Zeqing Li,2 Jing Yao,4 Sixia Chen,4 Ziyan Shen,4 Ganzhu Feng4 1Department of Infectious Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Kunshan, Suzhou, Jiangsu, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Respiratory Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ganzhu FengDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaTel +86-025-58509837Fax +86-025-58509994Email [email protected]: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice.Methods: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice.Results: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22.Conclusion: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.Keywords: A. baumannii, epitope vaccine, polymeric nanoparticles, PLGA, chitosan

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