Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting.

ABSTRACT: Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we show that an individual's first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows that protective HA imprinting is the crucial explanatory factor, and it provides 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and demonstrate that a novel strain's pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.

SUBMITTER: Gostic KM

PROVIDER: S-EPMC5134739 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting.

Gostic Katelyn M KM Ambrose Monique M Worobey Michael M Lloyd-Smith James O JO

Science (New York, N.Y.) 20161101 6313

Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we show that an individual's first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows that protective HA imprinting is the crucial explanatory factor, and it provides 75% protection against s ...[more]

PMID: 27846599

Similar Datasets

Antibodies to antigenic site A of influenza H7 hemagglutinin provide protection against H7N9 challenge.

Project description:Identifying major antigenic and protective epitopes of the H7 hemagglutinin (HA) will be important for understanding the antibody response to vaccines developed against the novel influenza H7N9 viruses that emerged in China in 2013. To facilitate antigenic characterization of the H7N9 HA and to develop reagents for evaluation of H7N9 candidate vaccines, we generated a panel of murine monoclonal antibodies (mAbs) to the HA of A/Shanghai/2/2013 using mammalian cell-derived virus-like particles (VLP) containing the H7 HA. Neutralizing antibodies identified an HA epitope corresponding to antigenic site A on the structurally similar influenza H3 hemagglutinin. Importantly, the neutralizing antibodies protect against A/Shanghai/2/2013 challenge. This antigenic site is conserved among many H7 viruses, including strains of both Eurasian and North American lineage, and the isolated neutralizing antibodies are cross-reactive with older H7 vaccine strains. The results indicate that the identified antigenic site is a potentially important protective epitope and suggest the potential benefit of cross-reactive antibody responses to vaccination with H7 candidate vaccines.

| S-EPMC4309539 | biostudies-literature

Influenza H7N9 Virus Hemagglutinin with T169A Mutation Possesses Enhanced Thermostability and Provides Effective Immune Protection against Lethal H7N9 Virus Challenge in Chickens.

Project description:H7N9 avian influenza virus (AIV) has caused huge losses in the poultry industry and impacted human public health security, and still poses a potential threat. Currently, immune prevention and control of avian influenza relies on traditional inactivated vaccines; however, they have some limitations and genetically engineered avian influenza subunit vaccines may be potential candidate vaccines. In this study, a T169A mutation in the HA protein derived from H7N9 AIV A/Chicken/Guangdong/16876 (H7N9-16876) was generated using the baculovirus expression system (BVES). The results showed that the mutant (HAm) had significantly increased thermostability compared with the wild-type HA protein (HA-WT). Importantly, immunizing chickens with HAm combined with ISA 71VG elicited higher cross-reactive hemagglutination inhibition (HI) antibody responses and cytokine (IFN-γ and IL-4) secretion. After a lethal challenge with heterologous H7N9 AIV, the vaccine conferred chickens with 100% (10/10) clinical protection and effectively inhibited viral shedding, with 90% (9/10) of the chickens showing no virus shedding. The thermostability of HAm may represent an advantage in practical vaccine manufacture and application. In general, the HAm generated in this study represents a promising subunit vaccine candidate for the prevention and control of H7N9 avian influenza.

| S-EPMC10460070 | biostudies-literature

An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

Project description:In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

| S-EPMC4417706 | biostudies-other

Proposed lead molecules against Hemagglutinin of avian influenza virus (H5N1).

Project description:Human infection with avian influenza H5N1 is an emerging infectious disease characterized by respiratory symptoms and a high fatality rate. Hemagglutinin and neuraminidase are the two surface proteins responsible for infection by influenza virus. Till date, neuraminidase has been the major target for antiviral drugs. In the present study we chose hemagglutinin protein as it mediates the binding of the virus to target cells through sialic acid residues on the host cell-surface. Hemagglutinin of H5 avian influenza (PDB ID: 1JSN) was used as the receptor protein. Ligands were generated by structure-based de novo approach and virtual screening of ZINC database. A total of 11,104 conformers were generated and docked into the receptor binding site using 'High Throughput Virtual Screening'. We proposed potential lead molecules against the receptor binding site of hemagglutinin based on the results obtained from in silico docking and hydrogen bond interaction between the ligand and the 1JSN protein molecule. We found sialic acid derivative 1 to be the lead molecules amongst the ligands generated by structure based de novo approach. However the molecules obtained from ZINC database were showing better docking scores as well as conserved hydrogen bond interactions. Thus we proposed ZINC00487720 and ZINC00046810 as potential lead molecules that could be used as an inhibitor to the receptor binding site of hemagglutinin. They could now be studied in vivo to validate the in silico results.

| S-EPMC2258429 | biostudies-literature

Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

Project description:H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

| S-EPMC5124960 | biostudies-literature

Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin.

Project description:Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 10(7) virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses.

| S-EPMC3065472 | biostudies-literature

Differences in the Epidemiology of Childhood Infections with Avian Influenza A H7N9 and H5N1 Viruses.

Project description:The difference between childhood infections with avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. We compared the epidemiological characteristics of 244 H5N1 and 41 H7N9 childhood cases (<15 years old), as well as the childhood cluster cases of the two viruses. Our findings revealed a higher proportion of H5N1 than H7N9 childhood infections (31.1% vs. 6.4%, p = 0.000). However, the two groups did not differ significantly in age (median age: 5.0 vs. 5.5 y, p = 0.0651). The proportion of clustered cases was significantly greater among children infected with H5N1 than among children infected with H7N9 [46.7% (71/152) vs. 23.6% (13/55), p = 0.005], and most of the childhood cases were identified as secondary cases [46.4% (45/97) vs. 33.3% (10/30), p = 0.000]. Mild status accounted for 79.49% and 22.66%, severe status for 17.95% and 2.34%, and fatal cases for 2.56% and 75.00% of the H7N9 and H5N1 childhood infection cases (all p<0.05), respectively. The fatality rates for the total, index and secondary childhood cluster cases were 52.86% (37/70), 88.5% (23/26) and 33.33% (15/45), respectively, in the H5N1 group, whereas no fatal H7N9 childhood cluster cases were identified. In conclusion, lower severity and greater transmission were found in the H7N9 childhood cases than in the H5N1 childhood cases.

| S-EPMC5047462 | biostudies-literature

Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.

Project description:Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

| S-EPMC6241527 | biostudies-literature

A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses.

Project description:H5N1 influenza viruses have spread extensively among wild birds and domestic poultry. Cross-species transmission of these viruses to humans has been documented in over 380 cases, with a mortality rate of approximately 60%. There is great concern that a H5N1 virus would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. An H5N1 influenza vaccine must, therefore, be an integral part of any pandemic preparedness plan. However, traditional methods of making influenza vaccines have yet to produce a candidate that could induce potently neutralizing antibodies against divergent strains of H5N1 influenza viruses. To address this need, we generated a consensus H5N1 hemagglutinin (HA) sequence based on data available in early 2006. This sequence was then optimized for protein expression before being inserted into a DNA plasmid (pCHA5). Immunizing mice with pCHA5, delivered intramuscularly via electroporation, elicited antibodies that neutralized a panel of virions that have been pseudotyped with the HA from various H5N1 viruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Moreover, immunization with pCHA5 in mice conferred complete (clades 1 and 2.2) or significant (clade 2.1) protection from H5N1 virus challenges. We conclude that this vaccine, based on a consensus HA, could induce broad protection against divergent H5N1 influenza viruses and thus warrants further study.

| S-EPMC2533225 | biostudies-other

A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.

Project description:The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.

| S-EPMC6290738 | 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