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In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

BACKGROUND: The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful se...

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Autores principales: Afshari, Elnaz, Cohan, Reza Ahangari, Sotoodehnejadnematalahi, Fattah, Mousavi, Seyed Fazlollah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830136/
https://www.ncbi.nlm.nih.gov/pubmed/36627666
http://dx.doi.org/10.1186/s12967-022-03864-z
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author Afshari, Elnaz
Cohan, Reza Ahangari
Sotoodehnejadnematalahi, Fattah
Mousavi, Seyed Fazlollah
author_facet Afshari, Elnaz
Cohan, Reza Ahangari
Sotoodehnejadnematalahi, Fattah
Mousavi, Seyed Fazlollah
author_sort Afshari, Elnaz
collection PubMed
description BACKGROUND: The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family. METHODS: To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA(1-5c+p) vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA(1-5c+p), we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA(1-5c+p) antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay. RESULTS: For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA(1-5c+p) protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA(1-5c+p) IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells. CONCLUSION: Our findings elucidated the potential application of the PspA(1-5c+p) vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA(1-5c+p) vaccine candidate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03864-z.
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spelling pubmed-98301362023-01-10 In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A Afshari, Elnaz Cohan, Reza Ahangari Sotoodehnejadnematalahi, Fattah Mousavi, Seyed Fazlollah J Transl Med Research BACKGROUND: The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family. METHODS: To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA(1-5c+p) vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA(1-5c+p), we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA(1-5c+p) antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay. RESULTS: For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA(1-5c+p) protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA(1-5c+p) IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells. CONCLUSION: Our findings elucidated the potential application of the PspA(1-5c+p) vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA(1-5c+p) vaccine candidate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03864-z. BioMed Central 2023-01-10 /pmc/articles/PMC9830136/ /pubmed/36627666 http://dx.doi.org/10.1186/s12967-022-03864-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Afshari, Elnaz
Cohan, Reza Ahangari
Sotoodehnejadnematalahi, Fattah
Mousavi, Seyed Fazlollah
In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
title In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
title_full In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
title_fullStr In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
title_full_unstemmed In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
title_short In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
title_sort in-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein a
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830136/
https://www.ncbi.nlm.nih.gov/pubmed/36627666
http://dx.doi.org/10.1186/s12967-022-03864-z
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