Dataset Information

Graph-theoretical formulation of the generalized epitope-based vaccine design problem.

ABSTRACT: Epitope-based vaccines have revolutionized vaccine research in the last decades. Due to their complex nature, bioinformatics plays a pivotal role in their development. However, existing algorithms address only specific parts of the design process or are unable to provide formal guarantees on the quality of the solution. We present a unifying formalism of the general epitope vaccine design problem that tackles all phases of the design process simultaneously and combines all prevalent design principles. We then demonstrate how to formulate the developed formalism as an integer linear program, which guarantees optimality of the designs. This makes it possible to explore new regions of the vaccine design space, analyze the trade-offs between the design phases, and balance the many requirements of vaccines.

SUBMITTER: Dorigatti E

PROVIDER: S-EPMC7652351 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Graph-theoretical formulation of the generalized epitope-based vaccine design problem.

Dorigatti Emilio E Schubert Benjamin B

PLoS computational biology 20201023 10

Epitope-based vaccines have revolutionized vaccine research in the last decades. Due to their complex nature, bioinformatics plays a pivotal role in their development. However, existing algorithms address only specific parts of the design process or are unable to provide formal guarantees on the quality of the solution. We present a unifying formalism of the general epitope vaccine design problem that tackles all phases of the design process simultaneously and combines all prevalent design princ ...[more]

PMID: 33095790

Similar Datasets

Project description:Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vaccination is believed to induce durable and protective responses against all the dengue virus (DENV) serotypes in order to reduce the burden posed by this virus, the development of a safe and efficacious vaccine remains a challenge. Immunoinformatics and computational vaccinology have been utilized in studies of infectious diseases to provide insight into the host-pathogen interactions thus justifying their use in vaccine development. Since vaccination is the best bet to reduce the burden posed by DENV, this study is aimed at developing a multi-epitope based vaccines for dengue control. Combined approaches of reverse vaccinology and immunoinformatics were utilized to design multi-epitope based vaccine from the sequence of DENV. Specifically, BCPreds and IEDB servers were used to predict the B-cell and T-cell epitopes, respectively. Molecular docking was carried out using Schrödinger, PATCHDOCK and FIREDOCK. Codon optimization and in silico cloning were done using JCAT and SnapGene respectively. Finally, the efficiency and stability of the designed vaccines were assessed by an in silico immune simulation and molecular dynamic simulation, respectively. The predicted epitopes were prioritized using in-house criteria. Four candidate vaccines (DV-1-4) were designed using suitable adjuvant and linkers in addition to the shortlisted epitopes. The binding interactions of these vaccines against the receptors TLR-2, TLR-4, MHC-1 and MHC-2 show that these candidate vaccines perfectly fit into the binding domains of the receptors. In addition, DV-1 has a better binding energies of - 60.07, - 63.40, - 69.89 kcal/mol against MHC-1, TLR-2, and TLR-4, with respect to the other vaccines. All the designed vaccines were highly antigenic, soluble, non-allergenic, non-toxic, flexible, and topologically assessable. The immune simulation analysis showed that DV-1 may elicit specific immune response against dengue virus. Moreover, codon optimization and in silico cloning validated the expressions of all the designed vaccines in E. coli. Finally, the molecular dynamic study shows that DV-1 is stable with minimum RMSF against TLR4. Immunoinformatics tools are now applied to screen genomes of interest for possible vaccine target. The designed vaccine candidates may be further experimentally investigated as potential vaccines capable of providing definitive preventive measure against dengue virus infection.

Dataset Information

Graph-theoretical formulation of the generalized epitope-based vaccine design problem.

Publications

Graph-theoretical formulation of the generalized epitope-based vaccine design problem.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets