title: Correlation between humoral and cellular immune responses and the expression of the hepatitis A receptor HAVcr-1 on T cells after hepatitis A re-vaccination in high and low-responder vaccinees.
abstract: BACKGROUND
  We recently published a study on the persistence of seroprotection 10 years after primary hepatitis A vaccination in an unselected study population of 1014 vaccinees. The majority of these vaccinees still exhibited sufficient protective antibody levels, while 2% displayed antibody concentrations below detection level. In order to investigate whether the low antibody levels were due to decline after primary vaccination or due to an intrinsic inability to sufficiently respond to hepatitis A antigen, we sought to recruit these low/no responder vaccinees to characterize their immune responses in more detail after booster vaccination in comparison to high responder vaccinees.
  
  
  METHODS
  Prior to and one week after booster vaccination with a hepatitis A vaccine, antibody levels, cytokine levels (IL-2, IFN-gamma and IL-10) and CD surface marker expression on peripheral blood mononuclear cells were determined in a study population comprised of 52 individuals. Additionally, the hepatitis A HAV cellular receptor 1 (HAVcr-1) TIM-1, being also expressed on CD4+ T cells and associated with immunomodulatory properties, was measured by RT-PCR before and after hepatitis A booster.
  
  
  RESULTS
  Our data indicate that there is indeed a small group of hepatitis A vaccinees that can be classified as low/no responders as their antibody levels remain below the seroprotection level of 20mIU/ml after booster vaccination. We further describe a good correlation between antibody concentrations and cellular responses, showing that low antibody production is associated with low antigen specific cytokine levels (IL-2, IFN-gamma, IL-10) and vice versa. While there was no significant difference in the expression of the most common surface markers on T and B cells before and after booster vaccination in low and high responder vaccinees, the expression of HAVcr-1 on CD4 T cells correlated significantly with the antibody responses and cytokine levels, suggesting this receptor as cellular prediction marker of immune responsiveness to hepatitis A.
  
  
  CONCLUSIONS
  Whether hepatitis A low/non-responders deserve particular attention as a risk group or might display certain resistance to hepatitis A infection due to a lack of the hepatitis A receptor needs further investigations. At this stage we suggest that persons at high exposure risk should be carefully observed.
authors.affiliation: Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erika
authors.initials: E
authors.lastname: Garner-Spitzer
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.forename: Pamela
authors.initials: P
authors.lastname: Rendi-Wagner
authors.forename: Birgit
authors.initials: B
authors.lastname: Winkler
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wiedermann
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Holzmann
authors.forename: Christian
authors.initials: C
authors.lastname: Herzog
authors.forename: Herwig
authors.initials: H
authors.lastname: Kollaritsch
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
mesh_terms: D000368:Aged; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006506:Hepatitis A / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D035922:Hepatitis A Antibodies / Q000097:blood*; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000072596:Hepatitis A Virus Cellular Receptor 1; D030041:Hepatitis A virus / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011991:Receptors, Virus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D016207:Cytokines; C491143:HAVCR1 protein, human; D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus