Immune Responses to H5N1 Vaccine With and Without AS03 Adjuvant

Adjuvants have been in use for many decades to enhance the effects of vaccines on the host
immune system, yet we know very little on how they actually work. Better understanding of the
mechanism by which adjuvants activate the immune system will enable us to develop better and
safer vaccines as well as a broad range of immune interventions to a wide spectrum of
diseases including cancer and autoimmunity.

In the current study we propose to study the effect of AS03 adjuvant on the innate/early
immune response to H5N1, avian flu, a potentially lethal disease that most subjects are
assumed to be naive to AS03 is an adjuvant oil in water emulsion containing
DL-alpha-tocopherol, squalene and the non-ionic detergent Tween 80 that has been widely used
as an adjuvant to flu vaccines produced by GlaxoSmithKline(GSK).

We therefore propose to randomize up to 60 healthy volunteers into two intervention arms (25
volunteers in each arm with up to 10 total replacements in the event a volunteer does not
return for the first vaccine). The first arm will receive a vaccine containing H5N1 with AS03
adjuvant, the second arm will receive H5N1 without AS03 adjuvant. Both arms will receive
primary and booster vaccination followed by repeated blood sampling to evaluate the immune
responses. We will apply high throughput analytic techniques and use systems biology methods
to integrate the collected data and draw a description of the immune system response with and
without the adjuvant.

The primary objective is to compare multiplex immune response signatures following two
(primary and a boost) vaccinations with the GSK AS03 adjuvanted H5N1 influenza vaccine, or
the non-adjuvanted form of the H5N1 influenza vaccine, at the 3.75 mcg dose and given 21 days
apart and identify differences in very early innate immune responses. These immune signatures
will also be correlated with the clinical observations especially safety related local and
systemic events.

- INCLUSION CRITERIA:

1. Healthy status confirmed by History, Physical Exam and blood work through the CHI
Screening Protocol.

2. Age 21 years to 45 years

3. Able to comprehend the investigational nature of the protocol and provide
informed consent

4. Must be willing to use effective birth control for one month before, during and
for two months after the last vaccination.

EXCLUSION CRITERIA:

1. Severe allergies to eggs or their products, chicken proteins or to any component of
the influenza antigen preparation.

2. Recipient of AS03 vaccine at any time in the past

3. Recipient of the seasonal influenza vaccine within the past 3 months.

4. Prior severe reactions to vaccines, including influenza vaccines (e.g. anaphylaxis,
angioedema or urticaria)

5. Participation on any blood collection or blood donation procedure during study that
will bring the total blood draw >550ml over 8 weeks

6. Current pregnancy (women of child bearing potential must have a negative serum
pregnancy test done on screening within 1 week of protocol accrual)

7. Currently breast-feeding

8. History of Guillain Barre syndrome

9. Acute illness with patient reported temperature of 38 (Infinite)C or greater within 3
days prior to the proposed time of administration.

10. Any history or presence of serious illness, bleeding disorders or autoimmune
disorders, or planned surgeries.

11. Weight less than 50 kg (110 pounds)

12. History of hepatitis or liver disease.

13. Subjects receiving immunosuppressive therapy.

14. Presence of HLA DQB1*06:02, the narcolepsy risk associated allele.