MBio: Influenza Virus Hemagglutinin Stalk-Specific Antibodies in Human Serum are a Surrogate Marker for In Vivo Protection in a Serum Transfer Mouse Challenge Model

[tetano]

Influenza Virus Hemagglutinin Stalk-Specific Antibodies in Human Serum are a Surrogate Marker for In Vivo Protection in a Serum Transfer Mouse Challenge Model

• Henning Jacobsen^a*,
• Madhusudan Rajendran^a,
• Angela Choi^a,^b,
• Haakon Sjursen^c,^d,
• Karl A. Brokstad^e,
• Rebecca J. Cox^d,^f,^g,
• Peter Palese^a,
• Florian Krammer^a,
• Raffael Nachbagauer^a

• ^aDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
• ^bGraduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
• ^cInfluenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway
• ^dSection for Infectious Diseases, Medical Department, Haukeland University Hospital, Bergen, Norway
• ^eDepartment of Clinical Science, Broeglemann Research Laboratory, University of Bergen, Bergen, Norway
• ^fKG Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, Norway
• ^gDepartment 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.

IMPORTANCE

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