Conglomeration of highly antigenic nucleoproteins to inaugurate a heterosubtypic next generation vaccine candidate against Arenaviridae family

Abstract

Arenaviral infections often resulting in lethal Hemorrhagic Fevers (HF) affect primarily African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapies. Hence, the study was employed to design a highly immunogenic heterosubtypic vaccine candidate against Arenaviridae family. The whole proteomes of Lassa virus (LASV), Lymphocytic Chorio Meningitis Virus (LCMV), Lujo virus and Guanarito virus were retrieved from NCBI database and assessed to determine the most antigenic viral proteins. Only the conserved sequences were used for T cell and B cell epitope prediction to ensure protective response against a wide range of viral strains. For each virus, nucleoproteins were identified as most antigenic which generated a plethora of antigenic epitopes. The proposed epitopes were highly conserved (up to 100%) and showed high cumulative population coverage. Moreover, results revealed that among the top epitopes, T cell epitope GWPYIGSRS were conserved in Argentine mammarenavirus (Junin virus) and Brazilian mammarenavirus (Sabia virus), while B cell epitope NLLYKICLSG were conserved in Bolivian mammarenavirus (Machupo virus) and Brazilian mammarenavirus (Sabia virus), indicating the possibility of final vaccine constructs to confer broad range immunity in the host. A total 3 constructs were designed by the combination of top epitopes from each protein along with suitable adjuvant and linkers. Different physicochemical properties revealed the superiority of construct V1 in terms of safety and efficacy. Docking analysis of the refined vaccine structure with different MHC molecules and human immune receptors were also biologically significant. The vaccine receptor complex (V1-TLR3) showed minimal deformability at molecular level. Moreover, construct V1 was compatible for insertion into pET28a(+) vector and heterologous cloning in E. coli srain K12. However, the results were based on different sequence analysis and various immune databases. Further wet lab based studies using model animals are highly recommended for the experimental validation of the designed vaccine candidates.

Genome based evolutionary lineage of SARS-CoV-2 towards the development of novel chimeric vaccine

“…Several linkers such as EAAAK, GGGS, GPGPG and KK in association with PADRE sequence were incorporated to construct fruitful vaccine sequences against COVID-19. The constructed vaccines were then analyzed whether they are non-allergenic by utilizing the following tool named Algpred ( Azim et al, 2019a , Azim et al, 2019b ). The most potential vaccine among the three constructs was then determined by assessing the antigenicity and solubility of the vaccines via VaxiJen v2.0 ( Doytchinova and Flower 2007b ) and Proso II server ( Smialowski et al, 2007 ), respectively.…”

“…In addition, peptide based subunit vaccines are biologically safer due to the absence of continuous in vitro culture during the production period, and also implies an appropriate activation of immune responses ( Purcell et al 2007 ; Dudek et al, 2010 ). Such immunoinformatic approaches have already been employed by the researchers to design vaccines against a number of deadly pathogens including Ebola virus ( Khan et al 2015 ), HIV ( Pandey et al 2018 ), Areanaviruses ( Azim et al 2019a ), Marburgvirus ( Hasan et al 2019a ), Norwalk virus ( Azim et al 2019b ), Nipah virus ( Saha et al 2017 ), Influenza virus ( Hasan et al 2019b ) and so on. At present, a suitable peptide vaccine to combat COVID-19 is urgently necessary that could efficiently generate enough immune response to destroy the virus.…”