Localized mucosal response to intranasal live attenuated influenza vaccine in adults

J Infect Dis. 2013 Jan 1;207(1):115-24. doi: 10.1093/infdis/jis641. Epub 2012 Oct 19.


Background: Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established.

Methods: Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses.

Results: Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination.

Conclusions: Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Viral / blood*
  • Cohort Studies
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dogs
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin A / biosynthesis
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza B virus / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Male
  • Middle Aged
  • Nasal Lavage Fluid / immunology
  • Vaccination
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology
  • Young Adult


  • Antibodies, Viral
  • Cytokines
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin A
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Vaccines, Inactivated
  • hemagglutinin, human influenza A virus