Seasonal Influenza Vaccination of Children Induces Humoral and Cell-Mediated Immunity Beyond the Current Season: Cross-reactivity With Past and Future Strains

J Infect Dis. 2016 Nov 15;214(10):1477-1486. doi: 10.1093/infdis/jiw380. Epub 2016 Aug 28.

Abstract

Background: Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection.

Methods: Children aged 9-14 years received 2010-2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains.

Results: 2010-2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010-2011) H3N2 component. Prior vaccination enhanced CD8+ T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009-2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ-secreting CD4+CD69+ T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009-2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α-secreting CD8+CD69+ T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010-2011 season than those who were not previously vaccinated.

Conclusions: Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season.

Keywords: B cell; T cell; children; cross-reactivity; hemagglutination inhibition; immune response; influenza; vaccine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Child
  • Cross Reactions
  • Female
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Male
  • Orthomyxoviridae / immunology*
  • T-Lymphocytes / immunology
  • Time Factors
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Inactivated