Midtveisevaluering - Mai Chi Trieu

Abstract

Introduction: Influenza vaccination is the main method of prophylaxis given
annually for seasonal influenza or during a pandemic. Healthcare workers (HCWs)
and other high-risk groups are recommended for annual influenza vaccination. Most
current influenza vaccines aim to induce neutralizing antibodies to prevent
infection. In the absence of protective antibodies against newly emerging influenza
viruses, cross reactive CD4+ and CD8+ T-cells can limit illness severity. However,
limited knowledge exists concerning the long-term effects of repeated vaccination
on both the humoral and cellular immune responses. When the 2009 pandemic
emerged with a novel H1N1pdm09 virus, it provided a unique opportunity to
address this key issue.

Methods: We followed up a unique cohort of HCWs (N=250) who had received a
single AS03-adjuvanted H1N1pdm09 vaccine in 2009 and subsequently either
repeated annual trivalent vaccination containing H1N1pdm09, H3N2 and B strains,
or no further vaccination between 2010 and 2013 (repeated or single groups,
respectively). Serum samples were collected pre- and post-vaccination (21 days, 3,
6 and 12 months) in the repeated group, or prior to the influenza season in the
single group to assess the antibody responses. Peripheral blood mononuclear cell
(PBMC) samples were collected pre- and post-vaccination (21 days and 12 months)
in season 2012/13 in the repeated group (n=13) or prior to the influenza season in
2012 and 2013 in the single group (n=12) to assess the T-cell responses.

Results: Antibodies were significantly induced following the H1N1pdm09
vaccination in 2009, waned over a year then significantly boosted following each
subsequent seasonal vaccination in the repeated group. Despite no boost from
seasonal vaccination, antibodies to H1N1pdm09 in the single group persisted above
the protective level over 5 years and did not differ from the repeated group.
Whereas, antibodies to H3N2 and B viruses were effectively induced following
vaccination in the repeated group and were significantly higher than that in the
single group. T-cell responses to H1N1pdm09 persisted up to 4 years after a single
pandemic vaccination, however, a trend of higher magnitude of T-cell responses
was observed following repeated vaccination. We have shown for the first time that
repeated vaccination maintains the cross-reactive IFN-γ+CD4+ and multi-cytokinesecreting
responses. The IFN-γ+CD8+ T-cells remained stable in both groups.

Conclusion: The AS03 adjuvant in the pandemic vaccine generated long-term
durable antibodies after a single vaccination, which has significant implications for
future vaccine design. The strain-specific antibodies were effectively induced
following each annual vaccination. Repeated vaccinations maintained strain-specific
antibodies and T-cells, and importantly, maintained cross-reactive IFN-γ+CD4+ and
CD8+ T-cells over time. Taken together, our study provides the immunological
evidence-base for continuing annual influenza vaccination policy in adults.