Immunogenicity of a Quadrivalent Virus-Like Particles (VLP) Influenza Vaccine in Healthy Adults

This randomized, observer-blind, multicenter, Phase 2 study will be conducted at multiple
sites across the United States and Canada.

The influenza strain composition of the Quadrivalent VLP Vaccine used in this study includes
2 influenza A virus strains (A/California/7/2009 [H1N1] and A/Switzerland/9715293/2013
[H3N2]) and 2 influenza B virus strains (B/Phuket/3073/2013 [Yamagata lineage] and
B/Brisbane/60/2008 [Victoria lineage]), based on the 2015-2016 recommended World Health
Organization (WHO) strains for vaccination in the Northern hemisphere.

Approximately 900 healthy subjects will be randomized in a 1:1:1 ratio to 1 of 3 parallel
treatment groups. Subjects in each group will be stratified into 2 age strata: 18 to 49
years and 50 to 64 years in a 2:1 ratio.

Subjects will receive one intramuscular (IM) injection of their assigned vaccine:

- 15 µg/strain of Quadrivalent VLP Vaccine, or

- 30 µg/strain of Quadrivalent VLP Vaccine, or

- 15 µg/strain of the licensed and commercially available quadrivalent vaccine FluLaval®
Tetra.

Subjects will participate in this study for approximately 8 months, during which 5 visits
will be scheduled, and phone contact will be made on Day 1, Day 8, and every 2 months
thereafter for up to 6 months post-Day 21 visit (Day 201). Safety laboratory assessments
will be performed at Screening, on Day 3 and within 48 hours of Day 3 results availability,
for grade 3 or grade 4 abnormalities or if deemed necessary by the investigator or early
termination.

Inclusion Criteria:

1. Subjects must be able to read, understand, and sign the informed consent form (ICF);
complete study-related procedures; and communicate with the study staff at visits and
by phone.

2. Subjects are considered by the Investigator to be reliable and likely to cooperate
with the assessment procedures and be available for the duration of the study.

3. Male and female subjects must be 18 to 64 years of age, inclusive, at Screening
(Visit 1).

4. Subjects have a body mass index (BMI) of ≥ 18.0 and ≤ 32.4 kg/m2 at Day 0.

5. Subjects must be in good general health prior to study participation (no more than 30
days prior to study vaccine administration) with no clinically relevant abnormalities
that could jeopardize subject safety or interfere with study assessments as assessed
by the Principal Investigator or sub-Investigator (thereafter referred as
Investigator) and determined by medical history, physical examination, biochemistry,
hematology, and urinalysis. Note: Subjects with a pre-existing chronic disease will
be allowed to participate if the disease is stable and, according to the
Investigator's judgment, the condition is unlikely to confound the results of the
study or pose additional risk to the subject by participating in the study. Stable
disease is generally defined as no new onset or exacerbation of pre-existing chronic
disease 6 months prior to immunization. Based on the Investigator's judgment, a
subject with more recent stabilization of a disease could also be eligible.

6. Female subjects must have a negative serum pregnancy test result at Screening (Visit
1) and a negative urine pregnancy test at Randomization prior to immunization.

7. Female subjects of childbearing potential must use an effective method of
contraception for 1 month prior to immunization and agrees to continue employing
adequate birth control measures for at least 60 days post-immunization. Moreover, she
must have no plan to become pregnant for at least 2 months post-immunization.
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.

The following relationship or methods of contraception are considered to be
effective:

- Hormonal contraceptives (e.g., injectable, topical [patch], or estrogenic
vaginal ring);

- Intra-uterine device with or without hormonal release;

- Male partner using a condom plus spermicide or sterilized partner (at least 1
year prior to immunization);

- Credible self-reported history of heterosexual abstinence until at least 60 days
postimmunization;

- Female partner.

8. Non-childbearing females are defined as:

- Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or
bilateral oophorectomy performed more than 1 month prior to immunization); or

- Post-menopausal (absence of menses for 24 consecutive months and age consistent
with natural cessation of ovulation).

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participating in
this study:

1. According to the Investigator's opinion, history of significant acute or chronic,
uncontrolled medical or neuropsychiatric illness. "Uncontrolled" is defined as:

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

- Requiring a change in medication dosage during one month prior to study vaccine
administration due to uncontrolled symptoms or drug toxicity, or for chronic
diseases, significant change in medication dosage within 6 months prior to study
vaccine administration based upon the investigator's judgment (elective dosage
adjustments in stable subjects are acceptable).

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 unable to
provide informed consent or unable to provide valid safety observations and
reporting.

3. Any autoimmune disease other than hypothyroidism on stable replacement therapy or any
confirmed or suspected immunosuppressive condition or immunodeficiency including
known or suspected human immunodeficiency virus (HIV), Hepatitis B or C infection, or
the presence of lymphoproliferative disease.

4. Administration or planned administration of any non-influenza vaccine within 30 days
prior to randomization up to blood sampling at Day 21. Immunization on an emergency
basis will be evaluated case-by-case by the Investigator.

5. Administration of any adjuvanted or investigational influenza vaccine within 1 year
prior to randomization or planned administration prior to the completion of Day 201.

6. Administration of any 'standard', non-adjuvanted influenza vaccine (e.g., live
attenuated trivalent/quadrivalent inactivated influenza vaccine Intranasal or split
trivalent/quadrivalent inactivated influenza vaccine by either intradermal or
intramuscular [IM] route) within 6 months prior to randomization and up to completion
of Day 21 visit.

7. Use of any investigational or non-registered product within 30 days or 5 half-lives,
whichever is longer, prior to randomization or planned use during the study period.
Subjects may not participate in any other investigational or marketed drug study
while participating in this study until Day 201 visit.

8. 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 immunoglobulin preparation within 3 months of
vaccination and until the completion of Day 21 visit. Low doses of nasal or inhaled
glucocorticoids are allowed. Topical steroids are permitted.

9. Any significant disorder of coagulation including treatment with warfarin derivatives
or heparin. Persons receiving prophylactic anti-platelet medications (e.g., low-dose
aspirin [no more than 325 mg/day]), and without a clinically apparent bleeding
tendency are eligible. Subjects treated with new generation drugs that do not
increase the risk of intramuscular bleeding (e.g., clopidogrel) are also eligible.

10. History of allergy to any of the constituents of the Quadrivalent VLP vaccine
(including H1N1, H3N2, B/Bris, and B/Phuket), to any components of the licensed
quadrivalent vaccine, or tobacco allergy.

11. History of anaphylactic allergic reactions to any food, medication, or bee sting.

12. Any history of serious asthma (e.g., status asthmaticus, hospitalization for asthma
control) or recurrent asthma episodes requiring medical attention in the last 3 years
(≥ 1 episode/year)

13. Continuous use of antihistamines in the last 4 weeks prior to immunization or use of
antihistamines 48 hours prior to study immunization.

14. Use of prophylactic medications (e.g. acetaminophen/paracetamol, aspirin, naproxen,
or ibuprofen) within 24 hours of randomization to prevent or pre-empt symptoms due to
vaccination. Subject discovered to have taken a prophylactic medication within the 24
hours prior to planned randomization must be delayed until at least the 24 hours
period is met.

15. Have a rash, dermatological condition, tattoos, muscle mass, or any other
abnormalities at injection site that may interfere with injection site reaction
rating.

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

17. If female subject, have a positive or doubtful pregnancy test result prior to
immunization or lactating females.

18. Have abnormal vital signs defined as: systolic Blood Pressure (BP) > 140 mmHg and/or
diastolic BP ≥ 90mmHg, heart rate ≤ 45 beats/min and ≥ 100 beats/min. Even if one or
more vital signs are out of the acceptable ranges, a subject may still be included in
the study based on Investigator's judgment (e.g. a resting heart rate ≤ 45 in
highly-trained athletes). Presence of any febrile illness (including oral temperature
(OT) ≥ 38.0 ˚C within 24 hours prior to immunization). Such subjects may be
re-evaluated for enrolment after resolution of illness.

19. 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. Person with non-treated, non-disseminated local prostate
cancer are eligible.

20. Identified as an Investigator or employee of the Investigator or clinical site with
direct involvement in the proposed study, or identified as an immediate family member
(i.e., parent, spouse, natural or adopted child) of the Investigator or employee with
direct involvement in the proposed study or any employees of Medicago.

21. Subject with a history of Guillain-Barre Syndrome.