NIH [to 23 April 2016]
http://www.nih.gov/news-events/news-releases

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April 19, 2016
NIH study finds factors that may influence influenza vaccine effectiveness
Long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
The long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited, new research suggests. Currently, seasonal flu vaccines are designed to induce high levels of protective antibodies against hemagglutinin (HA), a protein found on the surface of the influenza virus that enables the virus to enter a human cell and initiate infection. New research conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, found that higher levels of antibody against a different flu surface protein — neuraminidase (NA) — were the better predictor of protection against flu infection and its unpleasant side effects. Neuraminidase, which is not currently the main target antigen in traditional flu vaccines, enables newly formed flu viruses to exit the host cell and cause further viral replication in the body.

The findings, from a clinical trial in which healthy volunteers were willingly exposed to naturally occurring 2009 H1N1 influenza type A virus, appear online today in the open-access journal mBio (link is external):

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mBio
doi: 10.1128/mBio.00417-16
19 April 2016 mBio vol. 7 no. 2 e00417-16
Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model
Matthew J. Memolia, Pamela A. Shawb, Alison Hana, Lindsay Czajkowskia, Susan Reeda, Rani Athotaa, Tyler Bristola, Sarah Fargisa, Kyle Risosa, John H. Powersc, Richard T. Davey Jr.d, Jeffery K. Taubenbergera
Author Affiliations
aViral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
bPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
cDivision of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
dClinical Research Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
ABSTRACT
Despite long-term investment, influenza continues to be a significant worldwide problem. The cornerstone of protection remains vaccination, and approved vaccines seek to elicit a hemagglutination inhibition (HAI) titer of ≥1:40 as the primary correlate of protection. However, recent poor vaccine performance raises questions regarding the protection afforded and whether other correlates of protection should be targeted. A healthy volunteer challenge study was performed with a wild-type 2009 A(H1N1)pdm influenza A challenge virus at the NIH Clinical Center to evaluate two groups of participants with HAI titers of ≥1:40 and IMPORTANCE
This study represents the first time the current gold standard for evaluating influenza vaccines as set by the U.S. Food and Drug Administration and the European Medicines Agency Committee for Medicinal Products for Human Use, a “protective” hemagglutination inhibition (HAI) titer of ≥1:40, has been evaluated in a well-controlled healthy volunteer challenge study since the cutoff was established. We used our established wild-type influenza A healthy volunteer human challenge model to evaluate how well this antibody titer predicts a reduction in influenza virus-induced disease. We demonstrate that although higher HAI titer is predictive of some protection, there is stronger evidence to suggest that neuraminidase inhibition (NAI) titer is more predictive of protection and reduced disease. This is the first time NAI titer has been clearly identified in a controlled trial of this type to be an independent predictor of a reduction in all aspects of influenza.