Dataset Information

Influenza virus hemagglutinin stalk-based antibodies and vaccines.

ABSTRACT: Antibodies against the conserved stalk domain of the hemagglutinin are currently being discussed as promising therapeutic tools against influenza virus infections. Because of the conservation of the stalk domain these antibodies are able to broadly neutralize a wide spectrum of influenza virus strains and subtypes. Broadly protective vaccine candidates based on the epitopes of these antibodies, for example, chimeric and headless hemagglutinin structures, are currently under development and show promising results in animals models. These candidates could be developed into universal influenza virus vaccines that protect from infection with drifted seasonal as well as novel pandemic influenza virus strains therefore obviating the need for annual vaccination, and enhancing our pandemic preparedness.

SUBMITTER: Krammer F

PROVIDER: S-EPMC3804342 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Influenza virus hemagglutinin stalk-based antibodies and vaccines.

Krammer Florian F Palese Peter P

Current opinion in virology 20130824 5

Antibodies against the conserved stalk domain of the hemagglutinin are currently being discussed as promising therapeutic tools against influenza virus infections. Because of the conservation of the stalk domain these antibodies are able to broadly neutralize a wide spectrum of influenza virus strains and subtypes. Broadly protective vaccine candidates based on the epitopes of these antibodies, for example, chimeric and headless hemagglutinin structures, are currently under development and show ...[more]

PMID: 23978327

Similar Datasets

Project description:UnlabelledInfluenza remains a major global health burden. Seasonal vaccines offer protection but can be rendered less effective when the virus undergoes extensive antigenic drift. Antibodies that target the highly conserved hemagglutinin stalk can protect against drifted viruses, and vaccine constructs designed to induce such antibodies form the basis for a universal influenza virus vaccine approach. In this study, we analyzed baseline and postvaccination serum samples of children (6 to 59 months), adults (18 to 49 years), and elderly individuals (≥65 years) who participated in clinical trials with a recombinant hemagglutinin-based vaccine. We found that baseline IgG and IgA antibodies against the H1 stalk domain correlated with the ages of patients. Children generally had very low baseline titers and did not respond well to the vaccine in terms of making stalk-specific antibodies. Adults showed the highest induction of stalk-specific antibodies, but the elderly had the highest absolute antibody titers against the stalk. Importantly, the stalk antibodies measured by enzyme-linked immunosorbent assay (ELISA) showed neutralizing activity in neutralization assays and protected mice in a passive-transfer model in a stalk titer-dependent manner. Finally, we found similar patterns of stalk-specific antibodies directed against the H3 and influenza B virus hemagglutinins, albeit at lower levels than those measured against the H1 stalk. The relatively high levels of stalk-specific antibodies in the elderly patients may explain the previously reported low influenza virus infection rates in this age group. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.)ImportanceThe present study provides evidence that titers of broadly neutralizing hemagglutinin stalk-reactive antibodies increase with age, possibly due to repeated exposure to divergent influenza viruses. These relatively high levels of antistalk titers may be responsible for lower circulation rates of influenza viruses in older individuals. Our findings suggest that the level of antistalk antibodies is a good surrogate marker for protection against influenza virus infection. In addition, the levels of antistalk antibodies might determine the breadth of protection against different drifted strains.

Dataset Information

Influenza virus hemagglutinin stalk-based antibodies and vaccines.

Publications

Influenza virus hemagglutinin stalk-based antibodies and vaccines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets