New influenza A (H1N1) disease incidence and immunogenicity of the pandemic influenza A(H1N1) vaccine in healthy adults

Recently, pandemic H1N1 vaccines have been obtained by the government for the
entire Dutch population. However, at this point only the risk groups that also
recieve seasonal vaccination and health care workers, will recieve the vaccine.
We will investigate the incidence of pandemic influenza in vaccinated versus
unvaccinated individuals and the immunogenicity of the vaccine. This has
important implications for future influenza vaccination campaigns and for the
development of vaccines.

The WHO has just announced that the pandemic A/California/7/2009-like H1N1
vaccine strain will be included in the Northern Hemisphere 2010-2011 seasonal
vaccine, to replace the influenza A (H1N1) strain that was used before the
pandemic. This is the same strain that was used in the adjuvanted pandemic
influenza vaccine Focetria (2009).
The study will be extended for the duration of the next influenza season to
investigate long-term effects of the pandemic vaccine, either or not followed
by a seasonal vaccination (see next paragraph). New Informed Consent will be
obtained from participants for the extension.
The boosting capacity of the unadjuvanted seasonal vaccine, one year after
vaccination with the adjuvanted pandemic vaccine, will be evaluated. In
addition, long term immunogenicity will be measured one year after vaccination
with the pandemic vaccine. This will be done in pre-vaccination samples of the
group who will receive the seasonal 2010-2011 vaccine, but also in the
individuals who received the pandemic vaccine but do not wish to receive the
seasonal vaccine.
We will continue to measure influenza A (H1N1) incidence.

Primary: Evaluate new influenza A (H1N1) disease (pandemic influenza) incidence
of vaccinated compared to unvaccinated individuals.
Secondary:
* Obtain data on immunogenicity of pandemic influenza vaccination:
- Evaluation of the humoral immune response to the vaccine and correlate this
to protection against the virus.
- Evaluation of the cellular response to the vaccines and correlate this to
protection against the virus.
- Evaluation of the response to the second dose of the pandemic influenza
vaccine.

* Evaluation of cross-specific immune responses to pandemic H1N1 virus in the
pre-vaccination samples.
* Evaluation of specific immune responses against pandemic H1N1 virus in
infected, unvaccinated controls.

Added with reference to the extension:
* Obtain data on immunogenicity of adjuvanted pandemic influenza A (H1N1)
vaccination more than one year after vaccination
* Evaluation of the boosting capacity of unadjuvanted seasonal influenza A
(H1N1) vaccination
* Evaluation of humoral and cellular immune responses to influenza A (H3N2)
vaccin

Open, controlled, single-blinded, clinical trial with an authorized vaccine and
with invasive measurements.

Vaccination with pandemic influenza vaccine Focetria from Novartis.

Added with reference to the extension:
Voluntary vaccination with seasonal influenza vaccin 2010-2011.

The burden associated with participation is considered low. Participants are
vaccinated twice (not the control group). In the vaccinated group blood
samples are drawn (3 times 7 tubes, 60 ml, and 2 times 1 tube, 10 ml). In the
unvaccinated group 7 tubes, 60 ml blood samples are drawn twice.
Some attention is required for reporting of influenza-like illness. A nose
swab is taken from patients that report with influenza like illness.

The potential risks are considered minor. Subjects may experience adverse
reactions to the vaccine. Such adverse reactions are usually mild and of short
duration. The potential risks of venapuncture are mild pain and haematoma, and
are considered negligible. The taking of the nose swab in case of
influenza-like illness can be painful.
As a benefit, individual subjects in the vaccination arm of the trial are able
to obtain vaccination against pandemic influenza and may benefit from the
protection conferred by the vaccinations. There are no benefits for the
individual subjects in the unvaccinated group. The findings will have important
implications for future pandemic and seasonal influenza vaccination campaigns.
The results are possibly of benefit on a population level in the future.

Added with reference to the extension:
From participants who obtain the voluntary seasonal vaccine 2010-2011, three
additional blood samples are drawn (2 times 7 tubes, 60 ml, and 1 times 1
tube, 10 ml). From participants who do not obtain the voluntary seasonal
vaccine 2010-2011, two additional blood samples are drawn (2 times 7 tubes, 60
ml).