Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family
Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly im...
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Published in | Heliyon Vol. 7; no. 5; p. e07022 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Ltd
01.05.2021
Elsevier |
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Abstract | Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family using reverse vaccinology approach. The whole proteome of Lassa virus (LASV), Lymphocytic Choriomeningitis virus (LCMV), Lujo virus and Guanarito virus were retrieved and assessed to determine the most antigenic viral proteins. Both T-cell and B-cell epitopes were predicted and screened based on transmembrane topology, antigenicity, allergenicity, toxicity and molecular docking analysis. The final constructs were designed using different adjuvants, top epitopes, PADRE sequence and respective linkers and were assessed for the efficacy, safety, stability and molecular cloning purposes. The proposed epitopes were highly conserved (84%–100%) and showed greater cumulative population coverage. Moreover, T cell epitope GWPYIGSRS was conserved in Junin virus (Argentine mammarenavirus) and Sabia virus (Brazilian mammarenavirus), while B cell epitope NLLYKICLSG was conserved in Machupo virus (Bolivian mammarenavirus) and Sabia virus, indicating the possibility of final vaccine construct to confer a broad range immunity in the host. Docking analysis of the refined vaccine with different MHC molecules and human immune receptors were biologically significant. The vaccine-receptor (V1-TLR3) complex showed minimal deformability at molecular level and was compatible for cloning into pET28a(+) vector of E. coli strain K12. The study could be helpful in developing vaccine to combat arenaviral infections in the future. However, further in vitro and in vivo trials using model animals are highly recommended for the experimental validation of our findings.
Arenavirus; Hemorrhagic fevers; Nucleoprotein; Recombinant vaccine; Molecular docking |
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AbstractList | Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family using reverse vaccinology approach. The whole proteome of Lassa virus (LASV), Lymphocytic Choriomeningitis virus (LCMV), Lujo virus and Guanarito virus were retrieved and assessed to determine the most antigenic viral proteins. Both T-cell and B-cell epitopes were predicted and screened based on transmembrane topology, antigenicity, allergenicity, toxicity and molecular docking analysis. The final constructs were designed using different adjuvants, top epitopes, PADRE sequence and respective linkers and were assessed for the efficacy, safety, stability and molecular cloning purposes. The proposed epitopes were highly conserved (84%–100%) and showed greater cumulative population coverage. Moreover, T cell epitope GWPYIGSRS was conserved in Junin virus (Argentine mammarenavirus) and Sabia virus (Brazilian mammarenavirus), while B cell epitope NLLYKICLSG was conserved in Machupo virus (Bolivian mammarenavirus) and Sabia virus, indicating the possibility of final vaccine construct to confer a broad range immunity in the host. Docking analysis of the refined vaccine with different MHC molecules and human immune receptors were biologically significant. The vaccine-receptor (V1-TLR3) complex showed minimal deformability at molecular level and was compatible for cloning into pET28a(+) vector of
E. coli
strain K12. The study could be helpful in developing vaccine to combat arenaviral infections in the future. However, further
in vitro
and
in vivo
trials using model animals are highly recommended for the experimental validation of our findings.
Arenavirus; Hemorrhagic fevers; Nucleoprotein; Recombinant vaccine; Molecular docking Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family using reverse vaccinology approach. The whole proteome of Lassa virus (LASV), Lymphocytic Choriomeningitis virus (LCMV), Lujo virus and Guanarito virus were retrieved and assessed to determine the most antigenic viral proteins. Both T-cell and B-cell epitopes were predicted and screened based on transmembrane topology, antigenicity, allergenicity, toxicity and molecular docking analysis. The final constructs were designed using different adjuvants, top epitopes, PADRE sequence and respective linkers and were assessed for the efficacy, safety, stability and molecular cloning purposes. The proposed epitopes were highly conserved (84%–100%) and showed greater cumulative population coverage. Moreover, T cell epitope GWPYIGSRS was conserved in Junin virus (Argentine mammarenavirus) and Sabia virus (Brazilian mammarenavirus), while B cell epitope NLLYKICLSG was conserved in Machupo virus (Bolivian mammarenavirus) and Sabia virus, indicating the possibility of final vaccine construct to confer a broad range immunity in the host. Docking analysis of the refined vaccine with different MHC molecules and human immune receptors were biologically significant. The vaccine-receptor (V1-TLR3) complex showed minimal deformability at molecular level and was compatible for cloning into pET28a(+) vector of E. coli strain K12. The study could be helpful in developing vaccine to combat arenaviral infections in the future. However, further in vitro and in vivo trials using model animals are highly recommended for the experimental validation of our findings. Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family using reverse vaccinology approach. The whole proteome of Lassa virus (LASV), Lymphocytic Choriomeningitis virus (LCMV), Lujo virus and Guanarito virus were retrieved and assessed to determine the most antigenic viral proteins. Both T-cell and B-cell epitopes were predicted and screened based on transmembrane topology, antigenicity, allergenicity, toxicity and molecular docking analysis. The final constructs were designed using different adjuvants, top epitopes, PADRE sequence and respective linkers and were assessed for the efficacy, safety, stability and molecular cloning purposes. The proposed epitopes were highly conserved (84%–100%) and showed greater cumulative population coverage. Moreover, T cell epitope GWPYIGSRS was conserved in Junin virus (Argentine mammarenavirus) and Sabia virus (Brazilian mammarenavirus), while B cell epitope NLLYKICLSG was conserved in Machupo virus (Bolivian mammarenavirus) and Sabia virus, indicating the possibility of final vaccine construct to confer a broad range immunity in the host. Docking analysis of the refined vaccine with different MHC molecules and human immune receptors were biologically significant. The vaccine-receptor (V1-TLR3) complex showed minimal deformability at molecular level and was compatible for cloning into pET28a(+) vector of E. coli strain K12. The study could be helpful in developing vaccine to combat arenaviral infections in the future. However, further in vitro and in vivo trials using model animals are highly recommended for the experimental validation of our findings. Arenavirus; Hemorrhagic fevers; Nucleoprotein; Recombinant vaccine; Molecular docking |
ArticleNumber | e07022 |
Author | Azim, Kazi Faizul Akter, Rahima Bhuiyan, Omar Faruk Hia, Mantasha Mahmud Hasan, Mahmudul Hossain, Md Nazmul Lasker, Tahera |
Author_xml | – sequence: 1 givenname: Kazi Faizul surname: Azim fullname: Azim, Kazi Faizul organization: Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh – sequence: 2 givenname: Tahera surname: Lasker fullname: Lasker, Tahera organization: Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh – sequence: 3 givenname: Rahima surname: Akter fullname: Akter, Rahima organization: Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh – sequence: 4 givenname: Mantasha Mahmud surname: Hia fullname: Hia, Mantasha Mahmud organization: Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh – sequence: 5 givenname: Omar Faruk surname: Bhuiyan fullname: Bhuiyan, Omar Faruk organization: Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh – sequence: 6 givenname: Mahmudul surname: Hasan fullname: Hasan, Mahmudul organization: Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh – sequence: 7 givenname: Md Nazmul orcidid: 0000-0002-2192-0055 surname: Hossain fullname: Hossain, Md Nazmul email: nhossain.mib@sau.ac.bd organization: Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh |
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Keywords | Nucleoprotein Hemorrhagic fevers Recombinant vaccine Molecular docking Arenavirus |
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