Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

PLoS One. 2015 Nov 25;10(11):e0143281. doi: 10.1371/journal.pone.0143281. eCollection 2015.

Abstract

Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cytokines / metabolism
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity*
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A virus / immunology*
  • Influenza, Human / diagnosis
  • Influenza, Human / epidemiology*
  • Influenza, Human / immunology*
  • Male
  • Middle Aged
  • Neutralization Tests
  • Norway / epidemiology
  • Pandemics
  • Prospective Studies
  • Severity of Illness Index
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G

Grant support

The study was funded intramurally by the Influenza Centre at the University of Bergen, the Akershus University Hospital, and the Norwegian Institute of Public Health. Funding was received from the Bergen Clinical Vaccine Consortium and by the Ministry of Health and Care Services, Norway, the Norwegian Research Council Globvac program (220670), the Research Counsil Norway Bio bank (221122), the European Union (Univax 601738, Unisec 602012 and EU IMI115672 FLUCOP), Helse Vest and the K.G. Jebsen Centre for Research on Influenza Vaccines. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.