Early Induction of Cross-Reactive CD8+ T-Cell Responses in Tonsils After Live-Attenuated Influenza Vaccination in Children

J Infect Dis. 2020 Apr 7;221(9):1528-1537. doi: 10.1093/infdis/jiz583.

Abstract

Background: Live-attenuated influenza vaccine (LAIV) was licensed for prophylaxis of children 2-17 years old in Europe in 2012 and is administered as a nasal spray. Live-attenuated influenza vaccine induces both mucosal and systemic antibodies and systemic T-cell responses. Tonsils are the lymph nodes serving the upper respiratory tract, acting as both induction and effector site for mucosal immunity.

Methods: Here, we have studied the early tonsillar T-cell responses induced in children after LAIV. Thirty-nine children were immunized with trivalent LAIV (containing A/H1N1, A/H3N2, and B viruses) at days 3, 7, and 14 before tonsillectomy. Nonvaccinated controls were included for comparison. Tonsils and peripheral blood (pre- and postvaccination) were collected to study T-cell responses.

Results: Tonsillar and systemic T-cell responses differed between influenza strains, and both were found against H3N2 and B viruses, whereas only systemic responses were observed against A/H1N1. A significant increase in cross-reactive tonsillar CD8+ T cells recognizing conserved epitopes from a broad range of seasonal and pandemic viruses occurred at day 14. Tonsillar T cells showed significant cytokine responses (Th1, Th2, and granulocyte-macrophage colony-stimulating factor).

Conclusions: Our findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains.

Keywords: IFN-γ; LAIV; T cells; children; tonsils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / analysis*
  • CD8-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Cross Reactions
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • 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 / prevention & control*
  • Male
  • Norway
  • Palatine Tonsil / immunology*
  • Vaccination
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Attenuated