Dataset Information

Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy.

ABSTRACT:

Background

Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically naive and immunosuppressed patients. The prevention, diagnosis and therapy of HCMV infection are thus crucial to public health. The availability of effective prophylactic and therapeutic treatments remain a significant challenge and no vaccine is currently available. Here, we sought to define an epitope-based vaccine against HCMV, eliciting B and T cell responses, from experimentally defined HCMV-specific epitopes.

Results

We selected 398 and 790 experimentally validated HCMV-specific B and T cell epitopes, respectively, from available epitope resources and apply a knowledge-based approach in combination with immunoinformatic predictions to ensemble a universal vaccine against HCMV. The T cell component consists of 6 CD8 and 6 CD4 T cell epitopes that are conserved among HCMV strains. All CD8 T cell epitopes were reported to induce cytotoxic activity, are derived from early expressed genes and are predicted to provide population protection coverage over 97%. The CD4 T cell epitopes are derived from HCMV structural proteins and provide a population protection coverage over 92%. The B cell component consists of just 3 B cell epitopes from the ectodomain of glycoproteins L and H that are highly flexible and exposed to the solvent.

Conclusions

We have defined a multiantigenic epitope vaccine ensemble against the HCMV that should elicit T and B cell responses in the entire population. Importantly, although we arrived to this epitope ensemble with the help of computational predictions, the actual epitopes are not predicted but are known to be immunogenic.

SUBMITTER: Quinzo MJ

PROVIDER: S-EPMC6905002 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy.

Quinzo Monica J MJ Lafuente Esther M EM Zuluaga Pilar P Flower Darren R DR Reche Pedro A PA

BMC bioinformatics 20191210 Suppl 6

<h4>Background</h4>Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically naive and immunosuppressed patients. The prevention, diagnosis and therapy of HCMV infection are thus crucial to public health. The availability of effective prophylactic and therapeutic treatments remain a significant challenge and no vaccine is currently available. Here, we sought to define an epitope-based vaccine against HCMV, ...[more]

PMID: 31823715

Similar Datasets

Project description:IntroductionPneumococcus is an important respiratory pathogen that is associated with high rates of death in newborn children and the elderly. Given the disadvantages of current polysaccharide-based vaccines, the most promising alternative for developing improved vaccines may be to use protein antigens with different roles in pneumococcus virulence. PspA and PhtD, highly immunogenic surface proteins expressed by almost all pneumococcal strains, are capable of eliciting protective immunity against lethal infections.MethodsIn this study using immunoinformatics approaches, we constructed one fusion construct (called PAD) by fusing the immunodominant regions of PspA from families 1 & 2 (PA) to the immunodominant regions of PhtD (PD). The objective of this project was to test the immunogenicity of the fusion protein PAD and to compare its protective activity against S. pneumoniae infection with PA or PD alone and a combination of PA and PD. The prediction of physicochemical properties, antigenicity, allergenicity, toxicity, and 3D-structure of the constructs, as well as molecular docking with HLA receptor and immune simulation were performed using computational tools. Finally, mice were immunized and the serum levels of antibodies/cytokines and functionality of antibodies in vitro were evaluated after immunization. The mice survival rates and decrease of bacterial loads in the blood/spleen were examined following the challenge.ResultsThe computational analyses indicated the proposed constructs could be antigenic, non-allergenic, non-toxic, soluble and able to elicit robust immune responses. The results of actual animal experiments revealed the candidate vaccines could induce the mice to produce high levels of antibodies and cytokines. The complement-mediated bactericidal activity of antibodies was confirmed and the antibodies provided favorable survival in immunized mice after bacterial challenge. In general, the experimental results verified the immunoinformatics studies.ConclusionFor the first time this report presents novel peptide-based vaccine candidates consisting of immunodominant regions of PspA and PhtD antigens. The obtained findings confirmed that the fusion formulation could be relatively more efficient than the individual and combination formulations. The results propose that the fusion protein alone could be used as a serotype-independent pneumococcal vaccine or as an effective partner protein for a conjugate polysaccharide vaccine.

Project description:Porphyromonas gingivalis is a Gram-negative pathogenic bacterium associated with chronic periodontitis. The development of a chimeric peptide-based vaccine targeting this pathogen could be highly beneficial in preventing oral bone loss as well as other severe gum diseases. We applied a computational framework to design a multi-epitope-based vaccine candidate against P. gingivalis. The vaccine comprises epitopes from subunit proteins prioritized from the P. gingivalis reference strain (P. gingivalis ATCC 33277) using several reported vaccine properties. Protein-based subunit vaccines were prioritized through genomics techniques. Epitope prediction was performed using immunoinformatic servers and tools. Molecular modeling approaches were used to build a putative three-dimensional structure of the vaccine to understand its interactions with host immune cells through biophysical techniques such as molecular docking simulation studies and binding free energy methods. Genome subtraction identified 18 vaccine targets: six outer-membrane, nine cytoplasmic membrane-, one periplasmic, and two extracellular proteins. These proteins passed different vaccine checks required for the successful development of a vaccine candidate. The shortlisted proteins were subjected to immunoinformatic analysis to map B-cell derived T-cell epitopes, and antigenic, water-soluble, non-toxic, and good binders of DRB1*0101 were selected. The epitopes were then modeled into a multi-epitope peptide vaccine construct (linked epitopes plus adjuvant) to enhance immunogenicity and effectively engage both innate and adaptive immunity. Further, the molecular docking approach was used to determine the binding conformation of the vaccine to TLR2 innate immune receptor. Molecular dynamics simulations and binding free energy calculations of the vaccine-TLR2 complex were performed to highlight key intermolecular binding energies. Findings of this study will be useful for vaccine developers to design an effective vaccine for chronic periodontitis pathogens, specifically P. gingivalis.

Dataset Information

Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy.

Background

Results

Conclusions

Publications

Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets