tetano
Editor, Senior Moderator
[h=1]Influenza Virus Hemagglutinin Stalk-Specific Antibodies in Human Serum are a Surrogate Marker for In Vivo Protection in a Serum Transfer Mouse Challenge Model[/h]
[h=2]IMPORTANCE[/h] Influenza viruses are a serious concern for public health and cause a large number of deaths worldwide every year. Current influenza virus vaccines can confer protection from disease, but they often show low efficacy due to the ever-changing nature of the viruses. Novel vaccination approaches target conserved epitopes of the virus, including the hemagglutinin stalk domain, to elicit universally protective antibodies that also bind to mutated viruses or new subtypes of viruses. Importantly, the hemagglutination inhibition assay?the only assay that has been accepted as a correlate of protection by regulatory authorities?cannot measure antibodies against the hemagglutinin stalk domain. Therefore, novel correlates of protection and assays to measure vaccine immunogenicity need to be developed. In this study, we correlated the results from multiple assays with protection in mice after transfer of human serum and a lethal virus challenge to investigate potential novel serological surrogate markers for protection.
http://mbio.asm.org/content/8/5/e01463-17.executive-summary
- Henning Jacobsen[SUP]a[/SUP]*,
- Madhusudan Rajendran[SUP]a[/SUP],
- Angela Choi[SUP]a[/SUP],[SUP]b[/SUP],
- Haakon Sjursen[SUP]c[/SUP],[SUP]d[/SUP],
- Karl A. Brokstad[SUP]e[/SUP],
- Rebecca J. Cox[SUP]d[/SUP],[SUP]f[/SUP],[SUP]g[/SUP],
- Peter Palese[SUP]a[/SUP],
- Florian Krammer[SUP]a[/SUP],
- Raffael Nachbagauer[SUP]a[/SUP]
- [SUP]a[/SUP]Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- [SUP]b[/SUP]Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- [SUP]c[/SUP]Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
- [SUP]d[/SUP]Section for Infectious Diseases, Medical Department, Haukeland University Hospital, Bergen, Norway
- [SUP]e[/SUP]Department of Clinical Science, Broeglemann Research Laboratory, University of Bergen, Bergen, Norway
- [SUP]f[/SUP]KG Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, Norway
- [SUP]g[/SUP]Department of Research and Development, Haukeland University Hospital, Bergen, Norway
- Rino Rappuoli, Editor
- GSK Vaccines
- Address correspondence to Raffael Nachbagauer, raffael.nachbagauer{at}mssm.edu.
- ↵* Present address: Henning Jacobsen, Heinrich Pette Institute, Leibniz Institute of Experimental Virology, Hamburg, Germany.
[h=2]IMPORTANCE[/h] Influenza viruses are a serious concern for public health and cause a large number of deaths worldwide every year. Current influenza virus vaccines can confer protection from disease, but they often show low efficacy due to the ever-changing nature of the viruses. Novel vaccination approaches target conserved epitopes of the virus, including the hemagglutinin stalk domain, to elicit universally protective antibodies that also bind to mutated viruses or new subtypes of viruses. Importantly, the hemagglutination inhibition assay?the only assay that has been accepted as a correlate of protection by regulatory authorities?cannot measure antibodies against the hemagglutinin stalk domain. Therefore, novel correlates of protection and assays to measure vaccine immunogenicity need to be developed. In this study, we correlated the results from multiple assays with protection in mice after transfer of human serum and a lethal virus challenge to investigate potential novel serological surrogate markers for protection.
http://mbio.asm.org/content/8/5/e01463-17.executive-summary