Antibody Correlates and Predictors of Immunity to Naturally Occurring Influenza in Humans and the Importance of Antibody to the Neuraminidase

J Infect Dis. 2013 Mar 15;207(6):974-81. doi: 10.1093/infdis/jis935. Epub 2013 Jan 10.


Background: Serum antibody to the hemagglutinin (HA) of influenza viruses is a correlate and predictor of immunity to influenza in humans; the relative values of other correlates are uncertain.

Methods: Serum and nasal secretions (NS) were collected in fall and spring of 2009-2011 from healthy adults who were monitored for acute respiratory illness (ARI). Serum samples were tested for hemagglutination-inhibition (HAI) antibody increase and secretions for virus if ill; enrollment sera were also tested for neuraminidase-inhibiting (NI) antibody and NS for neutralizing (neut), NI, immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-HA antibody.

Results: Serum anti-HA and anti-neuraminidase (NA) antibody titers to 2009(H1N1) pandemic influenza virus (pH1N1) correlated with titers in NS (including IgA and IgG antibody). Increasing anti-HA and anti-NA titers in serum and NS tests all correlated with reducing infection and infection-associated illness. Multivariate analyses indicated serum HAI and NI each independently predicted immunity to infection and infection-associated illness. Only serum NI independently predicted reduced illness among infected subjects.

Conclusions: Increasing anti-HA and NA antibody in serum and secretions correlated with reducing pH1N1 influenza virus infection and illness in healthy young adults. Both anti-HA and anti-NA antibody are independent predictors of immunity to influenza; ensuring induction of both by vaccination is desirable.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Chi-Square Distribution
  • Female
  • Hemagglutination Inhibition Tests
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunoglobulin A / analysis
  • Immunoglobulin G / analysis
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / virology
  • Logistic Models
  • Male
  • Middle Aged
  • Nasal Lavage Fluid / chemistry
  • Nasal Lavage Fluid / immunology*
  • Nasal Lavage Fluid / virology
  • Neuraminidase / immunology*
  • Predictive Value of Tests
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Young Adult


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin A
  • Immunoglobulin G
  • Neuraminidase