Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets

Verma, Mansi; Bhatnagar, Shradha; Kumari, Kavita; Mittal, Nidhi; Sukhralia, Shivani; At, Shruthi Gopirajan; Dhanaraj, Premnath; Lal, Rup

doi:10.1016/j.gene.2019.02.001

Cited by 11 publications

(5 citation statements)

References 69 publications

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“…Moreover, pan-proteomic screening was used to identify immunogenic epitopes, not only within structural proteins but even in the nonstructural proteins of ASFV. The inclusion of nonstructural viral proteins in this study was influenced by recommendations from various studies on different viruses citing that numerous nonstructural proteins are involved in viral activity and can also trigger host immunity 35 , 36 . ASFV genome encodes over 100 non-structural proteins 37 , in which the functions of many of these proteins remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus

Simbulan,

Banico,

Sira

et al. 2024

Sci Rep

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Despite being identified over a hundred years ago, there is still no commercially available vaccine for the highly contagious and deadly African swine fever virus (ASFV). This study used immunoinformatics for the rapid and inexpensive designing of a safe and effective multi-epitope subunit vaccine for ASFV. A total of 18,858 proteins from 100 well-annotated ASFV proteomes were screened using various computational tools to identify potential epitopes, or peptides capable of triggering an immune response in swine. Proteins from genotypes I and II were prioritized for their involvement in the recent global ASFV outbreaks. The screened epitopes exhibited promising qualities that positioned them as effective components of the ASFV vaccine. They demonstrated antigenicity, immunogenicity, and cytokine-inducing properties indicating their ability to induce potent immune responses. They have strong binding affinities to multiple swine allele receptors suggesting a high likelihood of yielding more amplified responses. Moreover, they were non-allergenic and non-toxic, a crucial prerequisite for ensuring safety and minimizing any potential adverse effects when the vaccine is processed within the host. Integrated with an immunogenic 50S ribosomal protein adjuvant and linkers, the epitopes formed a 364-amino acid multi-epitope subunit vaccine. The ASFV vaccine construct exhibited notable immunogenicity in immune simulation and molecular docking analyses, and stable profiles in secondary and tertiary structure assessments. Moreover, this study designed an optimized codon for efficient translation of the ASFV vaccine construct into the Escherichia coli K-12 expression system using the pET28a(+) vector. Overall, both sequence and structural evaluations suggested the potential of the ASFV vaccine construct as a candidate for controlling and eradicating outbreaks caused by the pathogen.

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Section: Discussionmentioning

confidence: 99%

Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus

Simbulan,

Banico,

Sira

et al. 2024

Sci Rep

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“…They determined that the monovalent 9-mer T cell epitopes for each DENV serotype can be exploited to generate unique antibodies against dengue virus, as well as a chimeric common tetravalent vaccine candidate capable of covering any of the four dengue virus serotypes. Verma et al ( 2019 ) conducted a comparative genomes study of Dengue virus (DENV) to identify novel vaccine targets. They discovered 100% conserved epitopes in the envelope protein (RCPTQGE), the NS3 (SAAQRRGR, PGTSGSPI), the NS4A (QRTPQDNQL), the NS4B (LQAKATREAQKRA), and the NS5 (QRGSGQV) proteins in all DENV serotypes.…”

Section: Discussionmentioning

confidence: 99%

Design of Monovalent and Chimeric Tetravalent Dengue Vaccine Using an Immunoinformatics Approach

Dixit¹

2021

Int J Pept Res Ther

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An immunoinformatics technique was used to predict a monovalent amide immunogen candidate capable of producing therapeutic antibodies as well as a potent immunogen candidate capable of acting as a universal vaccination against all dengue fever virus serotypes. The capsid protein is an attractive goal for anti-DENV due to its position in the dengue existence cycle. The widely accessible immunological data, advances in antigenic peptide prediction using reverse vaccinology, and the introduction of molecular docking in immunoinformatics have directed vaccine manufacturing. The C-proteins of DENV-1-4 serotypes were known as antigens to assist with logical design. Binding epitopes for TC cells, TH cells, and B cells is predicted from structural dengue virus capsid proteins. Each T cell epitope of C-protein integrated with a B cell as a templet was used as a vaccine and produce antibodies in contrast to serotype of the dengue virus. A chimeric tetravalent vaccine was created by combining four vaccines, each representing four dengue serotypes, to serve as a standard vaccine candidate for all four Sero groups. The LKRARNRVS, RGFRKEIGR, KNGAIKVLR, and KAINVLRGF from dengue 1, dengue 2, dengue 3, and dengue 4 epitopes may be essential immunotherapeutic representatives for controlling outbreaks.

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“…This peptide is present in the fusion loop in domain II (DII) of the DENV E protein and is highly conserved in all four DENV serotypes [39]. The B cell epitope B2 is also highly conserved in all four DENV serotypes and was derived from the NS4A protein, which has been shown to induce B cell antibody responses in DENV-infected individuals [25,40].…”

Section: Discussionmentioning

confidence: 99%

“…Four multi-epitope peptides were constructed using two different B cell epitopes. The B1 epitope (VDRGWGNGCGLFGKG) was derived from the DENV E protein domain II and identified by Muthusamy et al (2016) using in silico prediction [ 24 ], whilst the B2 epitope (KQRTPQDNQLTYVVI) was derived from the NS4A protein and identified in silico by Verma et al (2019) [ 25 ]. In addition, two different universal T-helper epitopes were incorporated, which were the artificial pan-DR binding epitope known as PADRE (AKFVAAWTLKAAA) [ 26 ] and the chimeric MHC class II epitope, TpD (ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ), comprising epitopes that were derived from tetanus and diphtheria toxoids.…”

Section: Methodsmentioning

confidence: 99%

Enhancement of Tetravalent Immune Responses to Highly Conserved Epitopes of a Dengue Peptide Vaccine Conjugated to Polystyrene Nanoparticles

et al. 2020

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Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4) were designed by linking a universal T-helper epitope (PADRE or TpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1–NP4) were constructed. Mice immunized with NP1–NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1–P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT50. Among the four conjugated peptide nanovaccines, NP3 comprising the TpD T-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8+ T cell epitope and adjuvants to further improve the immunogenicity is warranted.

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Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets

Cited by 11 publications

References 69 publications

Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus

Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus

Design of Monovalent and Chimeric Tetravalent Dengue Vaccine Using an Immunoinformatics Approach

Enhancement of Tetravalent Immune Responses to Highly Conserved Epitopes of a Dengue Peptide Vaccine Conjugated to Polystyrene Nanoparticles

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