Serum Level of Antibodies Against Novel Acinetobacter Baumannii OmpA-selected Peptides in ICU Staff: Promise for the Future of Vaccine Development
-
Shadi Paydarfar
,
Mohammad Amin Abbasi
,
Ali Hashemi
,
Sodabe Taheri
,
Mojgan Bandehpour
,
Nariman Mosaffa
Abstract
Extensively drug-resistant Acinetobacter baumannii is considered one of the most dangerous threats to global health, requiring novel therapeutic interventions. The outer membrane protein A (OmpA) is an immunogenic agent that triggers immune responses. The current study evaluated serum antibody levels against previously determined immunogenic OmpA peptides from A baumannii in ICU staff.
Serum samples were collected from 62 ICU staff members (representing the exposed group), healthy controls (representing the nonexposed group), and patients with systemic lupus erythematosus (SLE) (as controls for nonspecific antibody reactions). After excluding the cross-reactive antibodies via Escherichia coli lysate pretreatment, all the samples were assessed in the vicinity of A baumannii lysate by enzyme-linked immunosorbent assay (ELISA). All the positive samples were assessed for interaction with previously designed and selected peptides using ELISA. The protective potential of positive serum antibodies was surveyed in vitro using an opsonophagocytic study.
The most antibody positive samples against one of the dominant peptides were determined in the ICU personnel (75%). SLE serum samples did not react with candidate peptides. The strongest positive reaction was observed in serum treatment with one of the OmpA peptides (No. 5) with significant differences compared to other designed peptides. Our findings showed that ICU samples have substantially higher antibody levels than the nonexposed group; Positive samples show strong results in the opsonophagocytosiis assay.
This study demonstrates A baumannii colonization at human mucosal surfaces, especially in exposed healthy workers. Novel OmpA-derived peptides could be used to identify immunogenic vaccine candidates. Therefore, more studies are needed before this peptide and antibody levels are used in diagnosis, prevention, or treatment.
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2. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: Emergence of a successful pathogen. Clin Microbiol Rev. 2008;21(3):538–82.
3. Howard A, Donoghue MO, Feeney A, Sleator RD. Acinetobacter baumannii An emerging opportunistic pathogen. 2012;(June):243–50.
4. Sato Y, Tansho-Nagakawa S, Ubagai T, Ono Y. Analysis of Immune Responses in Acinetobacter baumannii-Infected Klotho Knockout Mice: A Mouse Model of Acinetobacter baumannii Infection in Aged Hosts. Front Immunol. 2020;11:601614.
5. Kamuyu G, Cheng YS, Willcocks S, Kewcharoenwong C, Kiratisin P, Taylor PW, et al. Sequential Vaccination with Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses. Front Immunol. 2021;12.
6. Yeganeh O, Shabani M, Pakzad P, Mosaffa N, Hashemi A. Evaluation the reactivity of a peptide-based monoclonal antibody derived from OmpA with drug resistant pulsotypes of Acinetobacter baumannii as a potential therapeutic approach. Ann Clin Microbiol Antimicrob. 2022;21(1):1–13.
7. Yeganeh O, Shabani M, Pakzad P, Mosaffa N, Hashemi A. Evaluation the Reactivity of a Peptide-Based Monoclonal Antibody with Drug Resistant Pulsotypes of Acinetobacter Baumannii as Potential Therapeutic Approach. 2022 Jun 30;21(1):30.
8. Harris G, Kuo Lee R, Lam CK, Kanzaki G, Patel GB, Xu HH, et al. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain. Antimicrob Agents Chemother. 2013;57(8):3601–13.
9. Pagan JD, Kitaoka M, Anthony RM. Engineered sialylation of pathogenic antibodies in vivo attenuates autoimmune disease. Cell. 2018;172(3):564–77.
10. Carter PJ, Lazar GA. Next generation antibody drugs: pursuit of the’high-hanging fruit. Nat Rev Drug Discov. 2018;17(3):197–223.
11. Luo G, Lin L, Ibrahim AS, Baquir B, Pantapalangkoor P, Robert A, et al. Active and Passive Immunization Protects against Lethal, Extreme Drug Resistant-Acinetobacter baumannii Infection. 2012;7(1).
12. Chopra S, Torres-Ortiz M, Hokama L, Madrid P, Tanga M, Mortelmans K, et al. Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2010;65(12):2598–601.
13. Lin M-F, Lan C-Y. Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside. World J Clin Cases WJCC. 2014;2(12):787.
14. Garcia-Quintanilla M, R Pulido M, J McConnell M. First steps towards a vaccine against Acinetobacter baumannii. Curr Pharm Biotechnol. 2013;14(10):897–902.
15. Huang W, Yao Y, Long Q, Yang X, Sun W, Liu C, et al. Immunization against multidrug-resistant Acinetobacter baumannii effectively protects mice in both pneumonia and sepsis models. PLoS One. 2014;9(6):e100727.
16. Mehdinejadiani 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 (OmpA) antigenic peptides as vaccine candidate in immunized mice. Iran J Allergy, Asthma Immunol. 2019;21(2):655–63.
17. Mehdinejadiani K, Hashemi A, Bandehpour M, Rahmani H, Ranjbar MM, Yardel V, et al. 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):537–49.
18. Nafarieh T, Bandehpour M, Hashemi A, Taheri S, Yardel V, Jamaati H, et al. Identification of antigens from nosocomial Acinetobacter baumannii clinical isolates in sera from ICU staff and infected patients using the antigenome technique. World J Microbiol Biotechnol. 2017;33(10):1–8.
19. Klinman DM, Shirai A, Ishigatsubo Y. Polyclonal B cell activation and B cell cross-reactivity during autoantibody production in systemic lupus erythematosus. Immunobiol Proteins Pept VII. 1994;12(3):115–23.
20. Fabrizio C, Fulvia C, Carlo P, Laura M, Elisa M, Francesca M, et al. Systemic lupus erythematosus with and without anti-dsDNA antibodies: analysis from a large monocentric cohort. Mediators Inflamm. 2015;2015.
21. Fawcett PT, O’brien AE, Doughty RA. An adsorption procedure to increase the specificity of enzyme-linked immunosorbent assays for lyme disease without decreasing sensitivity. Arthritis \& Rheum Off J Am Coll Rheumatol. 1989;32(8):1041–4.
22. Fawcett PT, Gibney KM, Rose CD, Klein JD, Doughty RA. Adsorption with a soluble E. coli antigen fraction improves the specificity of ELISA tests for Lyme disease. J Rheumatol. 1991;18(5):705–8.
23. Abbanat D, Davies TA, Amsler K, He W, Fae K, Janssen S, et al. Development and qualification of an opsonophagocytic killing assay to assess immunogenicity of a bioconjugated Escherichia coli vaccine. Clin Vaccine Immunol. 2017;24(12):e00123--17.
24. Lamiable A, Thévenet P, Rey J, Vavrusa M, Derreumaux P, Tufféry P. PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex. Nucleic Acids Res. 2016;44(W1):W449–54.
25. Zhou P, Jin B, Li H, Huang S-Y. HPEPDOCK: a web server for blind peptide–protein docking based on a hierarchical algorithm. Nucleic Acids Res. 2018;46(W1):W443–50.
26. Romero-Steiner S, Libutti D, Pais LB, Dykes J, Anderson P, Whitin JC, et al. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin Diagnostic Lab Immunol. 1997;4(4):415–22.
27. Fleck RA, Romero-Steiner S, Nahm MH. Use of HL-60 cell line to measure opsonic capacity of pneumococcal antibodies. Clin Vaccine Immunol. 2005;12(1):19–27.
28. Kobayashi SD, Voyich JM, Buhl CL, Stahl RM, DeLeo FR. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: cell fate is regulated at the level of gene expression. Proc Natl Acad Sci. 2002;99(10):6901–6.
29. Nielsen TB, Pantapalangkoor P, Luna BM, Bruhn KW, Yan J, Dekitani K, et al. Monoclonal antibody protects against Acinetobacter baumannii infection by enhancing bacterial clearance and evading sepsis. J Infect Dis. 2017;216(4):489–501.
30. Al-Rawi NF. Detection of Antibodies Against Lipopolysaccharide of the two Species of Acinetobacter Which Isolated from Clinical Materials by Using Indirect Haemagglutination Test. Med J Tikrit. 2005;2(112):87–91.
31. Tay MZ, Wiehe K, Pollara J. Antibody-dependent cellular phagocytosis in antiviral immune responses. Front Immunol. 2019;10:332.
32. Yuan W-L, Shen Y-J, Deng D-Y. Sex bias of Acinetobacter baumannii nosocomial infection. Am J Infect Control. 2018;46(8):957–8.
33. Mosaffa N, Nafarieh T, Bandehpour M, Gachkar L, Taheri S, Hashemi A, et al. The study of serum antibody level in patients with Acinetobacter baumanni infection and comparing with healthy people and intensive care unit personnel. Pajoohandeh J. 2015;20(3):171–80.
34. Huang W, Zhang Q, Li W, Chen Y, Shu C, Li Q, et al. Anti-outer membrane vesicle antibodies increase antibiotic sensitivity of pan-drug-resistant Acinetobacter baumannii. Front Microbiol. 2019;10:1379.
35. Huang W, Yao Y, Wang S, Xia Y, Yang X, Long Q, et al. Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii. Sci Rep. 2016;6(1):1–12.
36. Paydarfar S, HASHEMI ALI, ABBASI MA, BANDEHPOUR M, Bakhtiari A, Tajik F, et al. Investigation of Preformed Design Acinetobacter Baumannii Outer Membrane Protein A Peptide Vaccine Candidate In Reaction With Serum Antibodies From Icu Staffs Members. 2021;
37. Grguric-Smith LM, Lee HH, Gandhi JA, Brennan MB, DeLeon-Rodriguez CM, Coelho C, et al. Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model. Front Microbiol. 2015;6:1134.
38. Kang M-J, Jang A-R, Park J-Y, Ahn J-H, Lee T-S, Kim D-Y, et al. IL-10 protects mice from the lung infection of Acinetobacter baumannii and contributes to bacterial clearance by regulating STAT3-mediated MARCO expression in macrophages. Front Immunol. 2020;11:270.
2. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: Emergence of a successful pathogen. Clin Microbiol Rev. 2008;21(3):538–82.
3. Howard A, Donoghue MO, Feeney A, Sleator RD. Acinetobacter baumannii An emerging opportunistic pathogen. 2012;(June):243–50.
4. Sato Y, Tansho-Nagakawa S, Ubagai T, Ono Y. Analysis of Immune Responses in Acinetobacter baumannii-Infected Klotho Knockout Mice: A Mouse Model of Acinetobacter baumannii Infection in Aged Hosts. Front Immunol. 2020;11:601614.
5. Kamuyu G, Cheng YS, Willcocks S, Kewcharoenwong C, Kiratisin P, Taylor PW, et al. Sequential Vaccination with Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses. Front Immunol. 2021;12.
6. Yeganeh O, Shabani M, Pakzad P, Mosaffa N, Hashemi A. Evaluation the reactivity of a peptide-based monoclonal antibody derived from OmpA with drug resistant pulsotypes of Acinetobacter baumannii as a potential therapeutic approach. Ann Clin Microbiol Antimicrob. 2022;21(1):1–13.
7. Yeganeh O, Shabani M, Pakzad P, Mosaffa N, Hashemi A. Evaluation the Reactivity of a Peptide-Based Monoclonal Antibody with Drug Resistant Pulsotypes of Acinetobacter Baumannii as Potential Therapeutic Approach. 2022 Jun 30;21(1):30.
8. Harris G, Kuo Lee R, Lam CK, Kanzaki G, Patel GB, Xu HH, et al. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain. Antimicrob Agents Chemother. 2013;57(8):3601–13.
9. Pagan JD, Kitaoka M, Anthony RM. Engineered sialylation of pathogenic antibodies in vivo attenuates autoimmune disease. Cell. 2018;172(3):564–77.
10. Carter PJ, Lazar GA. Next generation antibody drugs: pursuit of the’high-hanging fruit. Nat Rev Drug Discov. 2018;17(3):197–223.
11. Luo G, Lin L, Ibrahim AS, Baquir B, Pantapalangkoor P, Robert A, et al. Active and Passive Immunization Protects against Lethal, Extreme Drug Resistant-Acinetobacter baumannii Infection. 2012;7(1).
12. Chopra S, Torres-Ortiz M, Hokama L, Madrid P, Tanga M, Mortelmans K, et al. Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2010;65(12):2598–601.
13. Lin M-F, Lan C-Y. Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside. World J Clin Cases WJCC. 2014;2(12):787.
14. Garcia-Quintanilla M, R Pulido M, J McConnell M. First steps towards a vaccine against Acinetobacter baumannii. Curr Pharm Biotechnol. 2013;14(10):897–902.
15. Huang W, Yao Y, Long Q, Yang X, Sun W, Liu C, et al. Immunization against multidrug-resistant Acinetobacter baumannii effectively protects mice in both pneumonia and sepsis models. PLoS One. 2014;9(6):e100727.
16. Mehdinejadiani 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 (OmpA) antigenic peptides as vaccine candidate in immunized mice. Iran J Allergy, Asthma Immunol. 2019;21(2):655–63.
17. Mehdinejadiani K, Hashemi A, Bandehpour M, Rahmani H, Ranjbar MM, Yardel V, et al. 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):537–49.
18. Nafarieh T, Bandehpour M, Hashemi A, Taheri S, Yardel V, Jamaati H, et al. Identification of antigens from nosocomial Acinetobacter baumannii clinical isolates in sera from ICU staff and infected patients using the antigenome technique. World J Microbiol Biotechnol. 2017;33(10):1–8.
19. Klinman DM, Shirai A, Ishigatsubo Y. Polyclonal B cell activation and B cell cross-reactivity during autoantibody production in systemic lupus erythematosus. Immunobiol Proteins Pept VII. 1994;12(3):115–23.
20. Fabrizio C, Fulvia C, Carlo P, Laura M, Elisa M, Francesca M, et al. Systemic lupus erythematosus with and without anti-dsDNA antibodies: analysis from a large monocentric cohort. Mediators Inflamm. 2015;2015.
21. Fawcett PT, O’brien AE, Doughty RA. An adsorption procedure to increase the specificity of enzyme-linked immunosorbent assays for lyme disease without decreasing sensitivity. Arthritis \& Rheum Off J Am Coll Rheumatol. 1989;32(8):1041–4.
22. Fawcett PT, Gibney KM, Rose CD, Klein JD, Doughty RA. Adsorption with a soluble E. coli antigen fraction improves the specificity of ELISA tests for Lyme disease. J Rheumatol. 1991;18(5):705–8.
23. Abbanat D, Davies TA, Amsler K, He W, Fae K, Janssen S, et al. Development and qualification of an opsonophagocytic killing assay to assess immunogenicity of a bioconjugated Escherichia coli vaccine. Clin Vaccine Immunol. 2017;24(12):e00123--17.
24. Lamiable A, Thévenet P, Rey J, Vavrusa M, Derreumaux P, Tufféry P. PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex. Nucleic Acids Res. 2016;44(W1):W449–54.
25. Zhou P, Jin B, Li H, Huang S-Y. HPEPDOCK: a web server for blind peptide–protein docking based on a hierarchical algorithm. Nucleic Acids Res. 2018;46(W1):W443–50.
26. Romero-Steiner S, Libutti D, Pais LB, Dykes J, Anderson P, Whitin JC, et al. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin Diagnostic Lab Immunol. 1997;4(4):415–22.
27. Fleck RA, Romero-Steiner S, Nahm MH. Use of HL-60 cell line to measure opsonic capacity of pneumococcal antibodies. Clin Vaccine Immunol. 2005;12(1):19–27.
28. Kobayashi SD, Voyich JM, Buhl CL, Stahl RM, DeLeo FR. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: cell fate is regulated at the level of gene expression. Proc Natl Acad Sci. 2002;99(10):6901–6.
29. Nielsen TB, Pantapalangkoor P, Luna BM, Bruhn KW, Yan J, Dekitani K, et al. Monoclonal antibody protects against Acinetobacter baumannii infection by enhancing bacterial clearance and evading sepsis. J Infect Dis. 2017;216(4):489–501.
30. Al-Rawi NF. Detection of Antibodies Against Lipopolysaccharide of the two Species of Acinetobacter Which Isolated from Clinical Materials by Using Indirect Haemagglutination Test. Med J Tikrit. 2005;2(112):87–91.
31. Tay MZ, Wiehe K, Pollara J. Antibody-dependent cellular phagocytosis in antiviral immune responses. Front Immunol. 2019;10:332.
32. Yuan W-L, Shen Y-J, Deng D-Y. Sex bias of Acinetobacter baumannii nosocomial infection. Am J Infect Control. 2018;46(8):957–8.
33. Mosaffa N, Nafarieh T, Bandehpour M, Gachkar L, Taheri S, Hashemi A, et al. The study of serum antibody level in patients with Acinetobacter baumanni infection and comparing with healthy people and intensive care unit personnel. Pajoohandeh J. 2015;20(3):171–80.
34. Huang W, Zhang Q, Li W, Chen Y, Shu C, Li Q, et al. Anti-outer membrane vesicle antibodies increase antibiotic sensitivity of pan-drug-resistant Acinetobacter baumannii. Front Microbiol. 2019;10:1379.
35. Huang W, Yao Y, Wang S, Xia Y, Yang X, Long Q, et al. Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii. Sci Rep. 2016;6(1):1–12.
36. Paydarfar S, HASHEMI ALI, ABBASI MA, BANDEHPOUR M, Bakhtiari A, Tajik F, et al. Investigation of Preformed Design Acinetobacter Baumannii Outer Membrane Protein A Peptide Vaccine Candidate In Reaction With Serum Antibodies From Icu Staffs Members. 2021;
37. Grguric-Smith LM, Lee HH, Gandhi JA, Brennan MB, DeLeon-Rodriguez CM, Coelho C, et al. Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model. Front Microbiol. 2015;6:1134.
38. Kang M-J, Jang A-R, Park J-Y, Ahn J-H, Lee T-S, Kim D-Y, et al. IL-10 protects mice from the lung infection of Acinetobacter baumannii and contributes to bacterial clearance by regulating STAT3-mediated MARCO expression in macrophages. Front Immunol. 2020;11:270.
| Files | ||
| Issue | Vol 22 No 2 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i2.12676 | |
| Keywords | ||
| Acinetobacter baumannii ICU Omp-A derived peptides Serum antibodies | ||
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How to Cite
1.
Paydarfar S, Abbasi MA, Hashemi A, Taheri S, Bandehpour M, Mosaffa N. Serum Level of Antibodies Against Novel Acinetobacter Baumannii OmpA-selected Peptides in ICU Staff: Promise for the Future of Vaccine Development. Iran J Allergy Asthma Immunol. 2023;22(2):150-162.
