Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adversomics: a new paradigm for vaccine safety and design.

ABSTRACT: Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance--and thus to infectious disease prevention--worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine AEs, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term 'adversomics' was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine AEs/reactions, and outline a plan for the further development of this emerging research field.

SUBMITTER: Whitaker JA

PROVIDER: S-EPMC4630804 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Adversomics: a new paradigm for vaccine safety and design.

Whitaker Jennifer A JA Ovsyannikova Inna G IG Poland Gregory A GA

Expert review of vaccines 20150502 7

Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance--and thus to infectious disease prevention--worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine AEs, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. ...[more]

PMID: 25937189

Similar Datasets

Exploiting antigenic diversity for vaccine design: the chlamydia ArtJ paradigm.

Project description:We present an interdisciplinary approach that, by incorporating a range of experimental and computational techniques, allows the identification and characterization of functional/immunogenic domains. This approach has been applied to ArtJ, an arginine-binding protein whose orthologs in Chlamydiae trachomatis (CT ArtJ) and pneumoniae (CPn ArtJ) are shown to have different immunogenic properties despite a high sequence similarity (60% identity). We have solved the crystallographic structures of CT ArtJ and CPn ArtJ, which are found to display a type II transporter fold organized in two ?-? domains with the arginine-binding region at their interface. Although ArtJ is considered to belong to the periplasm, we found that both domains contain regions exposed on the bacterial surface. Moreover, we show that recombinant ArtJ binds to epithelial cells in vitro, suggesting a role for ArtJ in host-cell adhesion during Chlamydia infection. Experimental epitope mapping and computational analysis of physicochemical determinants of antibody recognition revealed that immunogenic epitopes reside mainly in the terminal (D1) domain of both CPn and CT ArtJ, whereas the surface properties of the respective binding-prone regions appear sufficiently different to assume divergent immunogenic behavior. Neutralization assays revealed that sera raised against CPn ArtJ D1 partially reduce both CPn and CT infectivity in vitro, suggesting that functional antibodies directed against this domain may potentially impair chlamydial infectivity. These findings suggest that the approach presented here, combining functional and structure-based analyses of evolutionary-related antigens can be a valuable tool for the identification of cross-species immunogenic epitopes for vaccine development.

| S-EPMC2943275 | biostudies-literature

A New Paradigm for Protein Design and Biological Self-Assembly.

Project description:Very few molecules with biological origins contain the element fluorine. Nature's inability to incorporate fluorine into biomolecules is related to the low concentration of free fluoride in sea and surface water. However, judicious introduction of fluorine into proteins, nucleic acids, lipids and carbohydrates has allowed mechanistic scrutiny of enzyme catalysis, control of protein oligomerization in membranes, clustered display of ligands on surfaces of living cells, and in increasing the protease stability of protein and peptide therapeutics.

| S-EPMC2786179 | biostudies-literature

New directions in nicotine vaccine design and use.

Project description:Clinical trials of nicotine vaccines suggest that they can enhance smoking cessation rates but do not reliably produce the consistently high serum antibody concentrations required. A wide array of next-generation strategies are being evaluated to enhance vaccine efficacy or provide antibody through other mechanisms. Protein conjugate vaccines may be improved by modifications of hapten or linker design or by optimizing hapten density. Conjugating hapten to viruslike particles or disrupted virus may allow exploitation of naturally occurring viral features associated with high immunogenicity. Conjugates that utilize different linker positions on nicotine can function as independent immunogens, so that using them in combination generates higher antibody concentrations than can be produced by a single immunogen. Nanoparticle vaccines, consisting of hapten, T cell help peptides, and adjuvants attached to a liposome or synthetic scaffold, are in the early stages of development. Nanoparticle vaccines offer the possibility of obtaining precise and consistent control of vaccine component stoichiometry and spacing and immunogen size and shape. Passive transfer of nicotine-specific monoclonal antibodies offers a greater control of antibody dose, the ability to give very high doses, and an immediate onset of action but is expensive and has a shorter duration of action than vaccines. Viral vector-mediated transfer of genes for antibody production can elicit high levels of antibody expression in animals and may present an alternative to vaccination or passive immunization if the long-term safety of this approach is confirmed. Next-generation immunotherapies are likely to be substantially more effective than first-generation vaccines.

| S-EPMC4047682 | biostudies-other

New Vaccine Design and Delivery Technologies.

Project description:Technological advances in immunology, protein design, and genetic delivery have unlocked new possibilities for vaccine concepts and delivery technologies that were previously inaccessible. These next-generation vaccine design efforts are particularly promising in their potential to provide solutions to challenging targets for which conventional approaches have proven ineffective-for example, a universal influenza vaccine. In this perspective, we discuss emerging approaches to vaccine design and engineering based on recent insights into immunology, structural biology, computational biology, and immunoengineering. We anticipate that these cutting-edge, interdisciplinary approaches will lead to breakthrough vaccine concepts for ever-evolving and (re)emerging influenza viruses, with important ramifications for global public health.

| S-EPMC6452296 | biostudies-literature

Investigating decision rules with a new experimental design: the EXACT paradigm.

Project description:In the decision-making field, it is important to distinguish between the perceptual process (how information is collected) and the decision rule (the strategy governing decision-making). We propose a new paradigm, called EXogenous ACcumulation Task (EXACT) to disentangle these two components. The paradigm consists of showing a horizontal gauge that represents the probability of receiving a reward at time t and increases with time. The participant is asked to press a button when they want to request a reward. Thus, the perceptual mechanism is hard-coded and does not need to be inferred from the data. Based on this paradigm, we compared four decision rules (Bayes Risk, Reward Rate, Reward/Accuracy, and Modified Reward Rate) and found that participants appeared to behave according to the Modified Reward Rate. We propose a new way of analysing the data by using the accuracy of responses, which can only be inferred in classic RT tasks. Our analysis suggests that several experimental findings such as RT distribution and its relationship with experimental conditions, usually deemed to be the result of a rise-to-threshold process, may be simply explained by the effect of the decision rule employed.

| S-EPMC4630306 | biostudies-literature

Engineering new mycobacterial vaccine design for HIV-TB pediatric vaccine vectored by lysine auxotroph of BCG.

Project description:In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)-mycobacterial shuttle plasmid p2auxo.HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG.HIVA(2auxo). We demonstrated that the episomal plasmid p2auxo.HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG.HIVA(2auxo) vaccine strain. The BCG.HIVA(2auxo) vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice-compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on "double" auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth.

| S-EPMC4362382 | biostudies-other

New templates for HIV-1 antibody-based vaccine design.

Project description:A current strategy for the design of neutralizing antibody-based vaccines to prevent HIV-1 transmission is that of reverse engineering, starting from a neutralizing antibody and working back to reconstruct its epitope by structure-based design technology. However, the field has been impeded by a lack of appropriate antibodies for use as templates. Recently, new antibodies have been described that may fulfil this role, invigorating the field.

| S-EPMC2990654 | biostudies-literature

Rational Design of Small Molecules as Vaccine Adjuvants

Project description:Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 24h by in-vivo intramuscularly administration of R848, SMIP-7.7, SMIP-7.8 and 4%DMSO controls. Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 6h by in-vivo intramuscularly administration of R848 and SMIP-7.2 in 1% DMSO, and SMIP-7.10 and SMIP-7.10+alum in Buffer.

2015-11-02 | E-MTAB-2948 | biostudies-arrayexpress

Identification of New Features from Known Bacterial Protective Vaccine Antigens Enhances Rational Vaccine Design.

Project description:With many protective vaccine antigens reported in the literature and verified experimentally, how to use the knowledge mined from these antigens to support rational vaccine design and study underlying design mechanism remains unclear. In order to address the problem, a systematic bioinformatics analysis was performed on 291 Gram-positive and Gram-negative bacterial protective antigens with experimental evidence manually curated in the Protegen database. The bioinformatics analyses evaluated included subcellular localization, adhesin probability, peptide signaling, transmembrane ?-helix and ?-barrel, conserved domain, Clusters of Orthologous Groups, and Gene Ontology functional annotations. Here we showed the critical role of adhesins, along with subcellular localization, peptide signaling, in predicting secreted extracellular or surface-exposed protective antigens, with mechanistic explanations supported by functional analysis. We also found a significant negative correlation of transmembrane ?-helix to antigen protectiveness in Gram-positive and Gram-negative pathogens, while a positive correlation of transmembrane ?-barrel was observed in Gram-negative pathogens. The commonly less-focused cytoplasmic and cytoplasmic membrane proteins could be potentially predicted with the help of other selection criteria such as adhesin probability and functional analysis. The significant findings in this study can support rational vaccine design and enhance our understanding of vaccine design mechanisms.

| S-EPMC5662880 | biostudies-literature

B-cell epitope peptide cancer vaccines: a new paradigm for combination immunotherapies with novel checkpoint peptide vaccine.

Project description:In light of the numerous US FDA-approved humanized monoclonal antibodies (mAbs) for cancer immunotherapy, it is surprising that the advancement of B-cell epitope vaccines designed to elicit a natural humoral polyclonal antibody response has not gained traction in the immune-oncology landscape. Passive immunotherapy with humanized mAbs (Trastuzumab [Herceptin®]; Pertuzumab [Perjeta®]) has provided clinical benefit to breast cancer patients, albeit with significant shortcomings including toxicity problems and resistance, high costs, sophisticated therapeutic regimen and long half-life. The role of B-cell humoral immunity in cancer is under appreciated and underdeveloped. We have advanced the idea of active immunotherapy with chimeric B-cell epitope peptides incorporating a 'promiscuous' T-cell epitope that elicits a polyclonal antibody response, which provides safe, cost-effective therapeutic advantage over mAbs. We have created a portfolio of validated B-cell peptide epitopes against multiple receptor tyrosine kinases (HER-1, HER-3, IGF-1R and VEGF). We have successfully translated two HER-2 combination B-cell peptide vaccines in Phase I and II clinical trials. We have recently developed an effective novel PD-1 vaccine. In this article, I will review our approaches and strategies that focus on B-cell epitope cancer vaccines.

| S-EPMC7426751 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data