T cell epitope based vaccine design while targeting outer capsid proteins of rotavirus strains infecting neonates: an immunoinformatics approach

Abstract

Gastrointestinal diarrhea is majorly caused by the rotavirus (RV) in the children who generally are under the age group of 5 years. WHO estimates that ∼95% of the children contract RV infection, by this age. The disease is highly contagious; notably in many cases, it is proven fatal with high mortality rates especially in the developing countries. In India alone, an estimated 145,000 yearly deaths occurs due to RV related gastrointestinal diarrhea. WHO pre-qualified vaccines that are available for RV are all live attenuated vaccines with modest efficacy range between 40 and 60%. Further, the risk of intussusceptions has been reported in some children on RV vaccination. Thus, in a quest to develop alternative candidate to overcome challenges associated with these oral vaccines, we chose immunoinformatics approach to design a multi-epitope vaccine (MEV) while targeting the outer capsid viral proteinsVP4 and VP7 of the neonatal strains of rotavirus. Interestingly, ten epitopes, that is, six CD8⁺T-cells and four CD4⁺T-cell epitopes were identified which were predicted to be antigenic, non-allergic, non-toxic and stable. These epitopes were then linked to adjuvants, linkers, and PADRE sequences to create a multi-epitope vaccine for RV. The in silico designed RV-MEV and human TLR5 complex displayed stable interactions during molecular dynamics simulations. Further, the immune simulation studies of RV-MEV corroborated that the vaccine candidate emerges as a promising immunogen. Future investigations while performing in vitro and in vivo analyses with designed RV-MEV construct are highly desirable to warrant the potential of this vaccine candidate in protective immunity against different strains of RVs infecting neonates.

Communicated by Ramaswamy H. Sarma

Keywords:

• Gastrointestinal diarrhea in children
• immunoinformatics
• immune simulation
• molecular docking
• MD simulation
• neonates
• rotavirus
• toll like receptors (TLRs)
• multi-epitope vaccine

Acknowledgments

L.C. and M.C. acknowledge the KAUST Core Labs and Supercomputing Laboratory for providing computational resources on the HPC platform Shaheen II. Team members from STEMskills Research and Education Lab Private Limited are acknowledged for the critical reading of manuscript and computational support.

Authors’ contributions

Conceptualization: M.C., and A.R.S., A.D.S.; Methodology, A.D.S., A.D.S., R.K.G.,V.K., A.F.C. and M.C.; Software, A.R.S., A.D.S. and A.F.C.; Validation, M.C., A.R.S., A.F.C; Formal Analysis, A.D.S., A.R.S., S.G., and M.C.; Investigation, M.C. and A.R.S.; Resources, L.C.; Data Curation, A.D.S., A.R.S., S.G., V.K. L.C., and M.C.; Writing—Original Draft Preparation, A.D.S., A.R.S. and M.C.; Writing—Review & Editing, M.C., R.K.G., A.R.S.; Visualization, M.C. and A.R.S.; Supervision, M.C. and A.R.S.; Project Administration, M.C. and A.R.S.; Funding Acquisition, L.C. and A.R.S. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare the following competing financial interest(s): Authors R.K.G. and A.R.S. were employed by the company STEMskills Research and Education Lab Private Limited, Faridabad, Haryana, India. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

The research carried out was supported by King Abdullah University of Science and Technology: BAS funding to L.C.