Safety, Tolerability and Immunogenicity of a Plant-made Seasonal Quadrivalent VLP Influenza Vaccine in Adults

The Phase 1 portion of this study will be a dose escalation, cohort staggering (slow
enrollment) for the 3 dose levels (low, medium or high dose level) with a placebo-controlled
group:

- Cohort 1: A first cohort of thirteen subjects (13) subjects will be randomized, of
these ten (10) will be dosed with the lowest dose of the quadrivalent VLP vaccine and
three (3) will receive a placebo. The 7-day safety data after the immunization will be
collected and reviewed by the Data and Safety Monitoring Board (DSMB) consisting of the
Principal Investigator (PI), the Sponsor's Medical Officer and one external medical
expert, prior to permitting immunization with the medium dose level.

- Cohort 2: A second cohort of thirteen subjects (13) subjects will be randomized; of
these, ten (10) will be dosed with the medium dose of the quadrivalent VLP vaccine and
three (3) will receive a placebo. The 7-day safety data after the immunization will be
collected and reviewed by the DSMB, prior to permitting immunization with the highest
dose.

- Cohort 3: A third cohort of fourteen subjects (14) subjects will be randomized; of
these ten (10) dosed with the high dose of the quadrivalent VLP vaccine and four (4)
will receive a placebo. The 7-day safety data after the immunization will be collected
and reviewed by the DSMB. If the 7-day post-immunization safety data of this cohort is
satisfactory according to the DSMB review, the Phase 2 portion of the study will
proceed.

The Phase 2 portion of this study will be an observer-blind, randomized, dose-ranging study
of the 3 different vaccine doses or a placebo. Therefore, the remaining 20 subjects per
vaccine dose will be dosed with the remaining 20 subjects of the placebo group.

Three (3) and 21 days after immunization, key safety (Day 3) and immunogenicity (Day 21)
data will be collected and analyzed. All subjects will be followed for safety until Day 201
(6-month follow up), regardless the phase of the study.

Inclusion Criteria:

1. Male and female adults, 18 to 49 years of age, inclusive.

2. Healthy as judged by the Investigator or designee and determined by medical history,
complete general history/symptom-directed physical examination, vital signs,
screening laboratories, and medical history conducted no more than 30 days prior to
study vaccine administration.

3. BMI of ≥18 and ≤32.

4. Comprehension of the study requirements, expressed availability for the required
study period, and ability to attend scheduled visits.

5. Accessible by phone on a consistent basis.

6. Give his/her consent to participate in this study (by signing the ICF). In the
opinion of the Investigator, competence and willingness to provide written, informed
consent for participation after reading the informed consent form. The subject must
have adequate opportunity to discuss the study with an Investigator or qualified
designee.

7. If female, have a negative serum pregnancy test result prior to immunization.

8. Female of childbearing potential (except subjects in a same sex relationship), must
use an effective birth control for the 28 days prior to immunization and must agree
to continue employing adequate birth control measures for at least 60 days
post-immunization and must have no plan to become pregnant for at least 60 days
post-immunization. Highly effective birth control includes hormonal contraceptives
(e.g., injectable, topical [patch], estrogenic vaginal ring, etc.), intra-uterine
device (IUD), abstinence (confirmed by Investigator), or male condom plus spermicide.
Abstinent subjects should be asked what method(s) they would use, should their
circumstances change, and subjects without a well-defined plan should be excluded.

Exclusion Criteria:

1. Presence of significant acute or chronic, uncontrolled medical or neuropsychiatric
illness. "Uncontrolled" is defined as:

1. Requiring a new medical or surgical treatment within one month prior to study
vaccine administration;

2. Requiring a change in medication dosage in one month prior to study vaccine
administration due to uncontrolled symptoms or drug toxicity (elective dosage
adjustments in stable subjects are acceptable);

3. Hospitalization or an event fulfilling the definition of a serious adverse event
within one month prior to study vaccine administration.

2. Any medical or neuropsychiatric condition or any history of excessive alcohol use or
drug abuse which, in the Investigator's opinion, would render the subject incompetent
to provide informed consent or unable to provide valid safety observations and
reporting.

3. Any confirmed or suspected immunosuppressive condition or immunodeficiency including
history of human immunodeficiency virus (HIV) infection, Hepatitis B or C, or the
presence of lymphoproliferative disease.

4. Presence of any febrile illness, oral temperature of >38.0˚C within 24 hours prior to
immunization. Such subjects may be re-evaluated for enrolment after resolution of
illness.

5. History of autoimmune disease.

6. Administration of any vaccine (including any other influenza vaccine) within 30 days
prior to study enrolment or planned administration within the period from the
vaccination up to blood sampling at Day 21 or within 30 days prior to blood sampling
at Day 201. Immunization on an emergency basis of a tetanus and diphtheria toxoids
adsorbed for adult use (Td) will be allowed provided the vaccine is not administered
within two weeks prior to study vaccine administration. Receipt of any other
emergency immunizations (e.g., rabies) will result in a case-by-case review by the
medical monitor of continued participation.

7. Administration of any adjuvanted or investigational influenza vaccine other than a
'simple' seasonal Trivalent influenza vaccine (TIV) or Quadrivalent influenza vaccine
(QIV) within 1 year prior to study enrolment or planned administration prior to the
end of this trial (Day 201).

8. Use of any investigational or non-registered product within 30 days prior to study
enrolment or planned use during the study period. Subjects may not participate in any
other investigational or marketed drug study while participating in this study.

9. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone per
day, or equivalent for more than 7 consecutive days or for 10 or more days in total,
within one month of study vaccine administration, any other cytotoxic or
immunosuppressant drug, or any globulin preparation within 3 months of vaccination.
Low doses of nasal or inhaled glucocorticoids are allowed.

10. Use of high dose inhaled steroids or oral and parenteral high dose steroid
medications. Nasal steroids are allowed.

11. Any significant disorder of coagulation or treatment with warfarin derivatives or
heparin. Persons receiving prophylactic anti-platelet medications, e.g., low-dose
aspirin [≤ 325 mg/day (1 regular adult aspirin) or ≤ 81 mg/day (1 baby aspirin)], and
without a clinically apparent bleeding tendency are eligible.

12. History of allergy to any of the constituents of the quadrivalent VLP study vaccine,
or to the Phosphate-buffered saline (PBS) (used as placebo).

13. History of severe allergic reactions (including anaphylaxis) to any food, medication
or bee sting or previous severe asthma.

14. History of tobacco allergy.

15. Continuous use of anti-histamines in the last 4 weeks prior to immunization or use of
anti-histamines 48 hours prior to study immunization.

16. Have a rash, dermatological condition, tattoos, or muscle mass at injection site
which may interfere with injection site reaction rating.

17. Have received a blood transfusion within 90 days prior to study vaccination.

18. If female, either known pregnancy or urine beta-human chorionic gonadotropin (β-hCG)
test results consistent with pregnancy during the screening period and prior to study
vaccine administration on Day 0.

19. Female subjects who are lactating.

20. Any vital sign abnormalities: systolic blood pressure, diastolic blood pressure,
resting heart rate not well controlled or according to the Investigator's opinion.

21. Cancer or treatment for cancer within 3 years of study vaccine administration.
Persons with a history of cancer who are disease-free without treatment for 3 years
or more are eligible. Persons with treated and uncomplicated basal cell carcinoma of
the skin are eligible.