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.
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.
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.
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.