Persistence of Antibodies to Influenza Hemagglutinin and Neuraminidase Following One or Two Years of Influenza Vaccination

J Infect Dis. 2015 Dec 15;212(12):1914-22. doi: 10.1093/infdis/jiv313. Epub 2015 May 26.


Background: Antibody titers to influenza hemagglutinin (HA) and neuraminidase (NA) surface antigens increase in the weeks after infection or vaccination, and decrease over time thereafter. However, the rate of decline has been debated.

Methods: Healthy adults participating in a randomized placebo-controlled trial of inactivated (IIV) and live-attenuated (LAIV) influenza vaccines provided blood specimens immediately prior to vaccination and at 1, 6, 12, and 18 months postvaccination. Approximately half had also been vaccinated in the prior year. Rates of hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titer decline in the absence of infection were estimated.

Results: HAI and NAI titers decreased slowly over 18 months; overall, a 2-fold decrease in antibody titer was estimated to take >600 days for all HA and NA targets. Rates of decline were fastest among IIV recipients, explained in part by faster declines with higher peak postvaccination titer. IIV and LAIV recipients vaccinated 2 consecutive years exhibited significantly lower HAI titers following vaccination in the second year, but rates of persistence were similar.

Conclusions: Antibody titers to influenza HA and NA antigens may persist over multiple seasons; however, antigenic drift of circulating viruses may still necessitate annual vaccination. Vaccine seroresponse may be impaired with repeated vaccination.

Keywords: antibody persistence; hemagglutinin; immune correlates; influenza; influenza vaccine; longevity of antibody; neuraminidase; serologic assays; waning.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Female
  • Healthy Volunteers
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunoassay
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Male
  • Middle Aged
  • Neuraminidase / immunology*
  • Placebos / administration & dosage
  • Time Factors
  • Vaccination / methods*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Young Adult


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Placebos
  • Vaccines, Attenuated
  • Neuraminidase