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Published on: May 6, 2015
T cell epitope based vaccine design while targeting outer capsid proteins of rotavirus strains infecting neonates: an
Arijit Das Sharma1, Ravneet Kaur Grewal2, Suresh Gorle2
1School of Bio-Engineering and Bio-Sciences, Lovely Professional University, Punjab, India.
Insights
Rotavirus (RV) causes severe diarrhea in young children. An immunoinformatics approach designed a multi-epitope vaccine (MEV) targeting RV outer proteins, showing promise in silico for improved protection.
Area of Science:
- Immunoinformatics
- Vaccine Design
- Computational Biology
Background:
- Rotavirus (RV) is a leading cause of severe gastrointestinal diarrhea in children under five, with high mortality rates in developing countries.
- Current live attenuated RV vaccines have modest efficacy (40-60%) and potential risks like intussusception.
- There is a critical need for alternative, safer, and more effective RV vaccine candidates.
Purpose of the Study:
- To design a novel multi-epitope vaccine (MEV) against neonatal rotavirus strains using an immunoinformatics approach.
- To identify and characterize potent T-cell epitopes from RV outer capsid proteins VP4 and VP7.
- To computationally evaluate the stability and immunogenicity of the designed RV-MEV.
Main Methods:
- Utilized immunoinformatics tools to identify antigenic, non-allergic, and non-toxic CD8+ and CD4+ T-cell epitopes from RV VP4 and VP7 proteins.
- Constructed a multi-epitope vaccine (RV-MEV) by linking selected epitopes with adjuvants, linkers, and PADRE sequences.
- Performed molecular dynamics simulations and immune simulations to assess the stability and potential immunogenicity of the RV-MEV.
Main Results:
- Identified ten promising epitopes (six CD8+, four CD4+) predicted to be safe and stable.
- The in silico designed RV-MEV demonstrated stable interactions with human TLR5.
- Immune simulation studies indicated that the RV-MEV is a potentially potent immunogen.
Conclusions:
- The in silico designed RV-MEV is a promising candidate for a next-generation rotavirus vaccine.
- Further in vitro and in vivo studies are warranted to validate the efficacy of this novel vaccine construct.
- This immunoinformatics approach offers a viable strategy for developing improved vaccines against rotavirus infections.
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.
