Multi valent DNA vaccine against group A human rotavirus: an in-silico investigation

Abstract

Gastroenteritis due to single rotavirus causes huge economic loss annually.Severity of rotaviral diarrhoea among children is primarily manifested by different combinations of G and P types. Rotavirus surveillance studies resulted in two ambitious globally licensed vaccine namely, Rotarix and RotaTaq and a few other.However, post-vaccination surveillance studies indicate, vaccine failure and other complications such as intussusception, environmental enteric dysfunction, etc.Herein, we design a multivalent DNA vaccine against rotavirus and tested its efficiency by using in silico tools. Two main neutralizing rotaviral antigens i.e, VP7 and VP8 were taken into account and respectively 390, 450 known sequences of different serogroup have been analyzed to obtain a consensus sequence for epitope prediction. Epitopes specific for MHC-I and -II were predicted using IEDB and chosen based on their best IC 50 value and CPR. A good binding profile with a monoclonal antibody specific for B-cell antigens is displayed by all epitopes they were found to be non-allergenic in the human host. Ethnic specificity of the epitopes is also within acceptable range except for South African and Central American populations. We use pBI-CMV1 bidirectional mammalian expression vector to design the DNA vaccine, where we stapled manually integrated epitopes for VP7 and VP8 at MCS1 and 2 respectively. In conclusion, this study provides a new set of data for a new DNA vaccine against rotavirus.

Vaccinomics Approach for Multi-Epitope Vaccine Design against Group A Rotavirus Using VP4 and VP7 Proteins

“…The current multivalent vaccine was designed primarily against VP4 and VP7 proteins, against which neutralizing antibodies produced in the body were hypothesized to target all RVA genotypes circulating worldwide [61]. In previously reported studies, Devi et al conducted a study on all structural and non-structural proteins of group A rotavirus, Dutta et al narrowed it to VP7 and VP8 proteins, Jafarpour et al limited theirs to VP4 and VP6 proteins, while, Shovu et al were in accordance with our study in which they designed a vaccine against VP4 and VP7 proteins but of group A rotavirus circulating in Bangladesh only [8,32,58,59]. Moreover, the conservancy of their epitopes was up to 80% while the conservancy percentage of our epitopes was reduced to 70% since most of the 80% of conserved epitopes were lost in allergenicity and toxicity screenings.…”

“…Immuno-informatics is one of the emerging fields in relation to vaccine design using reverse vaccinology especially in this era of evolving viruses and computational advances. Previous work on the in silico rotavirus vaccine has carried screenings of T-cell and B-cell epitopes which were used as a reference for this study [8,32,[58][59][60].…”

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

“…Thus, RdRp has always been a favorite drug target in antiviral therapeutic research [20]. Nowadays, different antiviral strategies such as, capping the virus particle which enables tethering it into the host epithelial cell membrane [21], designing a DNA vaccine against the major glycoproteins displayed outside the viral capsid protein [22], targeted delivery of miRNA [23], combination antiviral drug therapy [24], etc are commonly employed for therapeutic purposes. Results of the present study suggest that ATP binding domain and RNA-directed 5'-3' polymerase activity of the RdRp exist within 549 th to 776 th amino acid residues (GO:0003968) and this stretch of amino acids is crucial for RNA synthesis (Figure 3).…”

Current Update on Rotavirus in-Silico Multiepitope Vaccine Design

“…An additional report on the development of a multivalent DNA vaccine by Dutta 161 featured the utilization of both VP7 and VP8* consensus sequences for epitope screening. Evolutionary analysis of VP7 and VP8* rotavirus A proteins was conducted; consensus sequences were determined; and T-cell epitopes (MHC I and MHC II binding) were predicted by the IEDB tool.…”