title: Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection.
abstract: BACKGROUND
  Laboratory correlates of influenza vaccine protection can best be identified by examining people who are infected despite vaccination. While the importance of antibody to viral hemagglutinin (HA) has long been recognized, the level of protection contributed independently by antibody to viral neuraminidase (NA) has not been determined.
  
  
  METHODS
  Sera from a controlled trial of the efficacies of inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) were tested by hemagglutination inhibition (HAI) assay, microneutralization (MN) assay, and a newly standardized lectin-based neuraminidase inhibition (NAI) assay.
  
  
  RESULTS
  The NAI assay detected a vaccine response in 37% of IIV recipients, compared with 77% and 67% of participants in whom responses were detected by the HAI and MN assays, respectively. For LAIV recipients, the NAI, HAI, and MN assays detected responses in 6%, 21%, and 17%, respectively. In IIV recipients, as NAI assay titers rose, the frequency of infection fell, similar to patterns seen with HAI and MN assays. HAI and MN assay titers were highly correlated, but NAI assay titers exhibited less of a correlation. Analyses suggested an independent role for NAI antibody in protection, which was similar in the IIV, LAIV, and placebo groups.
  
  
  CONCLUSIONS
  While NAI antibody is not produced to a large extent in response to current IIV, it appears to have an independent role in protection. As new influenza vaccines are developed, NA content should be considered.
  
  
  BACKGROUND
  NCT00538512.
authors: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors: Arnold S
authors: AS
authors: Monto
authors: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors: Joshua G
authors: JG
authors: Petrie
authors: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors: Rachel T
authors: RT
authors: Cross
authors: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors: Emileigh
authors: E
authors: Johnson
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Merry
authors: M
authors: Liu
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Weimin
authors: W
authors: Zhong
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Min
authors: M
authors: Levine
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Jacqueline M
authors: JM
authors: Katz
authors: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors: Suzanne E
authors: SE
authors: Ohmit
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000276:immunology*; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000201:enzymology / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007136:Immunoglobulins; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D009439:Neuraminidase
keywords: clinical trial; hemagglutinin; immune correlates; influenza; influenza vaccine; neuraminidase; serologic assays; vaccine response