Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural Insights for Anti-Influenza Vaccine Design.

ABSTRACT: Influenza A virus are a persistent and significant threat to human health, and current vaccines do not provide sufficient protection due to antigenic drift, which allows influenza viruses to easily escape immune surveillance and antiviral drug activity. Influenza hemagglutinin (HA) is a glycoprotein needed for the entry of enveloped influenza viruses into host cells and is a potential target for anti-influenza humoral immune responses. In recent years, a number of broadly neutralizing antibodies (bnAbs) have been isolated, and their relative structural information obtained from the crystallization of influenza antigens in complex with bnAbs has provided some new insights into future influenza vaccine research. Here, we review the current knowledge of the HA-targeted bnAbs and the structure-based mechanisms contributing to neutralization. We also discuss the potential for this structure-based approach to overcome the challenge of obtaining a highly desired "universal" influenza vaccine, especially on small proteins and peptides.

SUBMITTER: Han L

PROVIDER: S-EPMC6458449 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Structural insights into the design of novel anti-influenza therapies.

Project description:A limited arsenal of therapies is currently available to tackle the emergence of a future influenza pandemic or even to deal effectively with the continual outbreaks of seasonal influenza. However, recent findings hold great promise for the design of novel vaccines and therapeutics, including the possibility of more universal treatments. Structural biology has been a major contributor to those advances, in particular through the many studies on influenza hemagglutinin (HA), the major surface antigen. HA's primary function is to enable the virus to enter host cells, and structural work has revealed the various HA conformational forms generated during the entry process. Other studies have explored how human broadly neutralizing antibodies (bnAbs), designed proteins, peptides and small molecules, can inhibit and neutralize the virus. Here we review milestones in HA structural biology and how the recent insights from bnAbs are paving the way to design novel vaccines and therapeutics.

| S-EPMC5930012 | biostudies-literature

Epitope analysis for influenza vaccine design.

Project description:Until now, design of the annual influenza vaccine has relied on phylogenetic or whole-sequence comparisons of the viral coat proteins hemagglutinin and neuraminidase, with vaccine effectiveness assumed to correlate monotonically to the vaccine-influenza sequence difference. We use a theory from statistical mechanics to quantify the non-monotonic immune response that results from antigenic drift in the epitopes of the hemagglutinin and neuraminidase proteins. The results explain the ineffectiveness of the 2003-2004 influenza vaccine in the United States and provide an accurate measure by which to optimize the effectiveness of future annual influenza vaccines.

| S-EPMC4482133 | biostudies-other

Structural insights into the broad protection against H1 influenza viruses by a computationally optimized hemagglutinin vaccine.

Project description:Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is a promising vaccine strategy to protect against a wide range of current and future influenza viruses. Though effective in preclinical studies, the mechanistic basis driving the broad reactivity of COBRA proteins remains to be elucidated. Here, we report the crystal structure of the COBRA HA termed P1 and identify antigenic and glycosylation properties that contribute to its immunogenicity. We further report the cryo-EM structure of the P1-elicited broadly neutralizing antibody 1F8 bound to COBRA P1, revealing 1F8 to recognize an atypical receptor binding site epitope via an unexpected mode of binding.

| S-EPMC10126545 | biostudies-literature

Structural Vaccinology for Viral Vaccine Design.

Project description:Although vaccines have proven pivotal against arrays of infectious viral diseases, there are still no effective vaccines against many viruses. New structural insights into the viral envelope, protein conformation, and antigenic epitopes can guide the design of novel vaccines against challenging viruses such as human immunodeficiency virus (HIV), hepatitis C virus, enterovirus A71, and dengue virus. Recent studies demonstrated that applications of this structural information can solve some of the vaccine conundrums. This review focuses on recent advances in structure-based vaccine design, or structural vaccinology, for novel and innovative viral vaccine design.

| S-EPMC6476906 | biostudies-literature

From Structural Studies to HCV Vaccine Design.

Project description:Hepatitis C virus (HCV) is a serious and growing public health problem despite recent developments of antiviral therapeutics. To achieve global elimination of HCV, an effective cross-genotype vaccine is needed. The failure of previous vaccination trials to elicit an effective cross-reactive immune response demands better vaccine antigens to induce a potent cross-neutralizing response to improve vaccine efficacy. HCV E1 and E2 envelope (Env) glycoproteins are the main targets for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. Therefore, a molecular-level understanding of the nAb responses against HCV is imperative for the rational design of cross-genotype vaccine antigens. Here we summarize the recent advances in structural studies of HCV Env and Env-nAb complexes and how they improve our understanding of immune recognition of HCV. We review the structural data defining HCV neutralization epitopes and conformational plasticity of the Env proteins, and the knowledge applicable to rational vaccine design.

| S-EPMC8147963 | biostudies-literature

Targeting B cell responses in universal influenza vaccine design.

Project description:Since its first administration in the 1940s, the influenza vaccine has provided tremendous relief against influenza infections. However, time has revealed the ultimate limit of the vaccine and the call for its reinvention has now come, just as we are beginning to appreciate the antibody immune responses vital in preventing infections. New strategies to design the influenza vaccine rely on selectively inducing broadly neutralizing antibodies that are specific for highly conserved viral epitopes. Such approaches take us away from the limited range of protection provided by current seasonal influenza vaccines and towards a future with a pan-influenza vaccine capable of providing universal strain coverage.

| S-EPMC3212832 | biostudies-literature

Recent progress in structure-based anti-influenza drug design.

Project description:Seasonal and pandemic influenza have caused high morbidity and mortality worldwide. Recent emergence of influenza A H5N1 and H1N1 strains has heightened concern, especially as a result of their drug resistance. The life cycle of influenza viruses has been well studied and nearly all the viral proteins are becoming potential therapeutic targets. In this review, we present an overview of recent progress in structure-based anti-influenza drug design, paying close attention to the increasing role of computation and strategies for overcoming drug resistance.

| S-EPMC3459301 | biostudies-literature

"Breathing" Hemagglutinin Reveals Cryptic Epitopes for Universal Influenza Vaccine Design.

Project description:A universal vaccine against influenza remains a critical target, and efforts have recently focused on the stem of the hemagglutinin glycoprotein. In this issue of Cell and a related Cell Host & Microbe article, three studies identify broad protective epitopes in the hemagglutinin head domain that are exposed by trimer "breathing."

| S-EPMC7112349 | biostudies-literature

Regression approaches in the test-negative study design for assessment of influenza vaccine effectiveness.

Project description:Influenza vaccination is the most practical means available for preventing influenza virus infection and is widely used in many countries. Because vaccine components and circulating strains frequently change, it is important to continually monitor vaccine effectiveness (VE). The test-negative design is frequently used to estimate VE. In this design, patients meeting the same clinical case definition are recruited and tested for influenza; those who test positive are the cases and those who test negative form the comparison group. When determining VE in these studies, the typical approach has been to use logistic regression, adjusting for potential confounders. Because vaccine coverage and influenza incidence change throughout the season, time is included among these confounders. While most studies use unconditional logistic regression, adjusting for time, an alternative approach is to use conditional logistic regression, matching on time. Here, we used simulation data to examine the potential for both regression approaches to permit accurate and robust estimates of VE. In situations where vaccine coverage changed during the influenza season, the conditional model and unconditional models adjusting for categorical week and using a spline function for week provided more accurate estimates. We illustrated the two approaches on data from a test-negative study of influenza VE against hospitalization in children in Hong Kong which resulted in the conditional logistic regression model providing the best fit to the data.

| S-EPMC5545127 | biostudies-other

Structural Insights into the Design of Synthetic Nanobody Libraries.

Project description:Single domain antibodies from camelids, or nanobodies, are a unique class of antibody fragments with several advantageous characteristics: small monomeric size, high stability and solubility and easy tailoring for multiple applications. Nanobodies are gaining increasing acceptance as diagnostic tools and promising therapeutic agents in cancer and other diseases. While most nanobodies are obtained from immunized animals of the camelid family, a few synthetic nanobody libraries constructed in recent years have shown the capability of generating high quality nanobodies in terms of affinity and stability. Since this synthetic approach has important advantages over the use of animals, the recent advances are indeed encouraging. Here we review over a dozen synthetic nanobody libraries reported so far and discuss the different approaches followed in their construction and validation, with an emphasis on framework and hypervariable loop design as critical issues defining their potential as high-class nanobody sources.

| S-EPMC9000494 | 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