Boosting of Cross-Reactive and Protection-Associated T Cells in Children After Live Attenuated Influenza Vaccination

J Infect Dis. 2017 May 15;215(10):1527-1535. doi: 10.1093/infdis/jix165.


Background: Live attenuated influenza vaccines (LAIVs) stimulate a multifaceted immune response including cellular immunity, which may provide protection against newly emerging strains. This study shows proof of concept that LAIVs boost preexisting, cross-reactive T cells in children to genetically diverse influenza A virus (IAV) strains to which the children had not been exposed.

Methods: We studied the long-term cross-reactive T-cell response in 14 trivalent LAIV-vaccinated children using the fluorescent immunospot assay (FluoroSpot) with heterologous H1N1 and H3N2 IAVs and CD8+ peptides from the internal proteins (matrix protein 1 [M1], nucleoprotein [NP], polymerase basic protein 1 [PB1]). Serum antibody responses were determined by means of hemagglutination inhibition assay. Blood samples were collected before vaccination and up to 1 year after vaccination.

Results: Preexisting cross-reactive T cells to genetically diverse IAV strains were found in the majority of the children, which were further boosted in 50% of them after receipt of LAIV. Further analyses of these T cells showed significant increases in CD8+ T cells, mainly dominated by NP-specific responses. After vaccination with LAIV, the youngest children showed the highest increase in T-cell responses.

Conclusion: LAIV boosts durable, cross-reactive T-cell responses in children and may have a clinically protective effect at the population level. LAIV may be a first step toward the desired universal influenza vaccine.

Keywords: Influenza; LAIV; T-cell; cellular immune response; children; cross-reactive; heterologous; protection.; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Child
  • Child, Preschool
  • Cross Protection / immunology*
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • T-Lymphocytes / immunology*
  • Vaccines, Attenuated / immunology*


  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Attenuated