Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches

Abstract

Rift Valley fever (RVF) is a viral disease caused by a member of the Bunyavirales family causing severe infections in humans. The RVF virus is an enveloped, negative-sense, single-stranded RNA virus that can infect both animals and humans. The symptoms associated with these infections span from minor (fever and headaches) to severe (meningoencephalitis and hemorrhagic fever syndrome) symptoms. Despite the outbreaks of the RVF virus being reported in different parts of the world, no effective therapy is available. Herein, the development of an efficient vaccine is critical for the control of infections associated with the RVF virus. Moreover, computational vaccine approaches are helpful in the design of specific, safe, and stable peptide-based designs when compared to the conventional methods of vaccine development. In this study, the whole proteome of the virus, comprising four proteins (NP, L, GP, and NSP), was screened to find putative vaccine epitope sequences (T cell, B cell, and HTL) specific for each protein. These shortlisted epitopes were then combined with flexible linkers to design protein-specific and proteome-wide immunogenic multi-epitope-based vaccine constructs. The results revealed that these multi-epitope vaccine constructs (MEVCs) are strongly antigenic and non-allergenic in nature. The efficacy of these constructs was further validated by docking with immune receptors, which revealed strong binding interactions with human TLR8. Using the MD simulation approach, the binding stability and residual flexibility of the best vaccine construct (proteome-wide) were confirmed, which revealed stable dynamic and favorable features. Furthermore, in-silico cloning and immune simulation analysis confirmed the expression and production of immune factors, that is, IgM, IgG, and IL-6, against the proposed vaccine designs. Additionally, 3D models of all the MEVC constructs have been developed and evaluated for potential immunization against the RVF virus. Finally, the proteome-wide vaccine candidate (MEVC-PW-RVFV) with the highest immune reinforcement potential provides new insights into the development of future vaccines against the emerging RVF virus.

Proteomics-based vaccine targets annotation and design of multi-epitope vaccine against antibiotic-resistant Streptococcus gallolyticus

“…Three linkers, successfully utilized by Israr et al 72 , Ahtisham et al 73 , Naveed et al 74 , 75 , and Alizadeh et al 76 , were used to adjoin the selected epitopes together. The AAY (Ala-Ala-Tyr) linker is the cleavage site for proteasomes in mammalian cells.…”

Rapid and simultaneous multiepitope antigen-based detection of Enterococcus by microscale thermophoresis and immunomagnetic separation

“… Mahdevar et al (2022) designed a novel multi-epitope vaccine against breast cancer, which comprised of the most immunodominant epitope of the BORIS cancer-testis antigen by using immune-informatics approach. Albutti (2022) designed a multi-epitope vaccine structure that targets highly specific antigenic epitopes of the four target proteins of Rift Valley fever (RVF) and evaluated its potential immune effect, thus providing a new direction for future vaccines against RVF virus. Accordingly, the use of immune-informatics methods for the design of multi-epitope vaccines with high practical value has been become an attractive means of vaccine research, thus providing support for the prevention of many diseases in the future ( Molina-Franky et al, 2020 ; Saha et al, 2022 ).…”