Original Article
 

Evaluationof the New Outer Membrane Protein A Epitope-based Vaccines for Mice Model of Acinetobacter baumannii Associated Pneumonia and Sepsis Infection

Abstract

Nosocomial infections caused by Acinetobacter baumannii (A. baumannii) nosocomial infections caused by Acinetobacter baumannii (A. baumannii) are considered as a global serious problem in hospitalized patients because of emerging antibiotic resistance. Immunotherapy approaches are promising to prevent such infections. In our previous study, five antigenic epitopes of outer membrane protein A (OmpA), as the most dangerous virulence molecule in A. baumanii, were predicted in silico. In this study, the investigators evaluated some immunological aspects of the peptides.
Five peptides were separately injected into C5BL/6 mice; then the cytokine production (interleukin-4 and interferon-gamma) of splenocytes and opsonophagocytic activity of immunized serum were assessed. To identify the protective function of the peptides, animal models of sepsis and pneumonia infections were actively and passively immunized with selected peptides and pooled sera of immunized mice, respectively. Then, survival rates of them were compared with the non-infected controls. Based on the results, activated spleen cells in P127 peptide-immunized mice exhibited an increase level of IFN-γ compared with the other experimental groups, but not about the IL-4 concentration. The results of opsonophagocytic assay revealed an appropriate killing activity of produced antibodies against A. baumannii in a dose-dependent manner. Further, the survival rates of the mice under passive immunization with the immunized sera or active immunization with P127 peptide were significantly more than those in the control group. Moreover, the survival rate of the P127 peptide immunized group was considerably higher than that among the other peptide-immunized group.
In conclusion, findings indicated that peptides derived from outer membrane protein-A can be used as a promising tool for designing the epitope-based vaccines against infections caused by A. baumannii.  

1. Revelas AJ. Healthcare–associated infections: A public health problem. Niger Med J. 2012;53(2):59-65.
2. Baier C, Linke L, Eder M, Schwab F, Chaberny IF, Vonberg R-P, et al. Incidence, risk factors and healthcare costs of central line-associated nosocomial bloodstream infections in hematologic and oncologic patients. PLo S One. 2020;15(1):e0227772.
3. Howard AJV, Donoghue M, Feeney A, Sleator RD. Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence. 2012;3(3):243-50.
4. Munier A-L, Biard L, Legrand M, Rousseau C, Lafaurie M, Donay J-L, et al. Incidence, risk factors and outcome of multi-drug resistant Acinetobacter baumannii nosocomial infections during an outbreak in a burn unit.Int J Infect Dis. 2019;79:179-84.
5. Zeighami H, Valadkhani F, Shapouri R, Samadi E, Haghi FJBid. Virulence characteristics of multidrug resistant biofilm forming Acinetobacter baumannii isolated from intensive care unit patients.BMC Infect Dis. 2019;19(1):629.
6. Tala Ballouz, Jad Aridi, Claude Afif, Jihad Irani, Chantal Lakis, Rakan Nasreddine et al .Risk Factors, Clinical Presentationand Outcome of Acinetobacter baumannii Bacteremia..Front Cell Infect Microbiol. 2017;7:156.
7. Wangxue Chen. Host Innate Immune Responses to Acinetobacter baumannii Infection .Front Cell Infect Microbiol. 2020;10:486.
8. Zihe Yan, Junjun Yang, Renjing Hu, Xichi Hu, Kong Chen..Acinetobacter baumannii Infection andIL-17 Mediated Immunity.Med Inflmm .2016;2016:9834020.
9. Chang-Ro Lee, Jung Hun Lee, Moonhee Park, Kwang Seung Park , Kwon Bae, Young Bae Kim, et al.Biology of Acinetobacter baumannii:Pathogenesis, Antibiotic ResistanceMechanisms, and ProspectiveTreatment Options.FrontCellInfect Microbiol.Front Cell Infect Microbiol. 2017;7:55.
10. María Guadalupe García-Patiño, Rodolfo García-Contreras, and Paula Licona-Limón.The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections.Front Immunol. 2017;8(2):441-5.
11. Brittany L. Mortensen and Eric P. Skaar .Host–microbe interactions that shape the pathogenesis of Acinetobacter baumannii infection .Cell Microbiol. 2012;14(9):1336–44.
12. Dan Niel, Yue Hu1, Zhou Chen, Mingkai Li, Zheng Hou, Xiaoxing Luo, Xinggang Mao and Xiaoyan Xue. Outer membrane protein A (OmpA) as potential therapeutic target forAcinetobacter baumannii infection.J Biomed Sci. 2020;27(1):26-9.
13. Danilo G Moriel, Scott A Beatson, Daniël J Wurpe, Jeffrey Lipman, Graeme R Nimmo, David L Paterson, Mark A Schembri.Identification of novel vaccine candidates against multidrug-resistant Acinetobacter baumannii. PLo S ONE. 2013;8(10):e77631.
14. Yang Zhang, Jie Su and Donghui Wu. Physiology and pathology of Multidrug-Resistant Bacteria:Antibodies and Vaccines-Based Pathogen Specific Targeting. Physiology pathology of Immunology. 2018. INTEC.open/science. Chapter:10. Pages:199-230.http://dx.doi.org/10.5772/intechopen.70488
15. Mehdinezhadiani K,Bandehpour M, Hashemi A, Ranjbar MM, Taheri S, Jalali SA, et al. In silico Design and evaluation of Acinetobacter baumannii Outer Membrane Protein a Antigenic Peptides as Vaccine Candidate in Immunized Mice. Iran J Allergy Asthma Immunol. 2019;18(6):655-663.
16. Guanpingshen Luo, Lin Lin,Ashraf S Ibrahim1, Beverlie Baquir, Paul Pantapalangkoor, Robert A.Bonomo, et al. Active and Passive Immunization Protects against
Lethal, Extreme Drug Resistant-Acinetobacter baumanniiInfection. PLoS ONE. 20127(1):e29446.
17. Weiwei Huang, Yufeng Yao, Qiong Long, Xu Yang, Wenjia Sun, Cunbao Liu, et al. Immunization against multidrug-resistant Acinetobacter baumannii effectively protects mice in both pneumonia and sepsis models. PLoS ONE. 2014;9(6):e100727.
18. Perez F, Bonomo RAJV. Vaccines for Acinetobacter baumannii: thinking “out of the box”.Vaccine. 2014;32(22):2537-9.
19. Ainsworth S, Ketter PM, Yu J-J, Grimm RC, May HC, Cap AP, et al. Vaccination with a live attenuated Acinetobacter baumannii deficient in thioredoxin provides protection against systemic Acinetobacter infection.Vaccine. 2017;35(26):3387-94.
20. Sheweita S, Batah A, Ghazy A, Hussein A, Amara AJJoI, Health P. A new strain of Acinetobacter baumannii and characterization of its ghost as a candidate vaccine. J Infect Public Health. 2019;12(6):831-42.
21. Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro MJAom. Understanding modern-day vaccines: what you need to know. Ann Med. 2018;50(2):110-20.
22. Ahmad TA, Tawfik DM, Sheweita SA, Haroun M, El-Sayed LHJTiV. Development of immunization trials against Acinetobacter baumannii. Trial Vaccinol. 2016;5(2):53-60.
23. Lei L, Yang F, Zou J, Jing H, Zhang J, Xu W, et al. DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection. Mol Biol Rep. 2019;46(5):5397-408.
24. Parvizpour S, Pourseif MM, Razmara J, Rafi MA, Omidi YJDDT. Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches. Drug Discov Today. 2020;25(6):1034-42.
25. Nie D, Hu Y, Chen Z, Li M, Hou Z, Luo X, et al. Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection. BMC. 2020;27(1):26-9.
26. Luo G, Lin L, Ibrahim AS, Baquir B, Pantapalangkoor P, Bonomo RA, et al. Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection. PLoS One. 2012;7(1):e29446.
27. Lin L, Tan B, Pantapalangkoor P, Ho T, Hujer AM, Taracila MA, et al. Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes.Vaccine. 2013;31(2):313-8.
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IssueVol 20 No 5 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v20i5.7404
Keywords
Acinetobacter baumannii Outer membrane proteins Peptides Pneumonia Sepsis Vaccines

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How to Cite
1.
Mehdinejadiani K, Hashemi A, Bandehpour M, Rahmani H, Ranjbar M, Yardel V, Jalali SA, Mosaffa N. Evaluationof the New Outer Membrane Protein A Epitope-based Vaccines for Mice Model of Acinetobacter baumannii Associated Pneumonia and Sepsis Infection. Iran J Allergy Asthma Immunol. 2021;20(5):537-549.