Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family

Kazi Faizul Azim; Tahera Lasker; Rahima Akter; Mantasha Mahmud Hia; Omar Faruk Bhuiyan; Mahmudul Hasan; Md Nazmul Hossain

doi:10.1016/j.heliyon.2021.e07022

Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family

Heliyon. 2021 May 19;7(5):e07022. doi: 10.1016/j.heliyon.2021.e07022. eCollection 2021 May.

Authors

Kazi Faizul Azim^{1

2}, Tahera Lasker¹, Rahima Akter¹, Mantasha Mahmud Hia¹, Omar Faruk Bhuiyan³, Mahmudul Hasan^{1

4}, Md Nazmul Hossain^{1

2}

Affiliations

¹ Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
² Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
³ Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.
⁴ Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh.

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.

Keywords: Arenavirus; Hemorrhagic fevers; Molecular docking; Nucleoprotein; Recombinant vaccine.