Immunogenicity and Safety of 2 Doses of Avian Influenza A (H5N1) Vaccine Administered 3 vs. 8 Weeks Apart

• H5N1 vaccine (Arepanrix) (Biological), also known as Arepanrix, GSK: The H5N1 (Arepanrix) vaccine will be administered according to the Product Monograph.
• Saline (as a placebo) (Other), also known as Normal Saline: Normal saline will be administered as a placebo according to the Product Monograph.

Primary outcomes

• Percentages of participants with seroprotection against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart [28 days post-administration of 2 doses of avian influenza A (H5N1 (Approximately week 12).]: Percentages of participants with seroprotection against the H5N1 2.3.4.4b clade 28 days following administration of 2 doses of avian influenza A(H5N1) vaccine given 3 vs. 8 weeks apart based on serologic outcomes at visit 4 (approximately week 12). Seroprotection is defined as the proportion of subjects who were either seronegative prior to vaccination and have a protective post-vaccination HI titre of ≥ 1:40 or who were seropositive prior to vaccination and have at least a 4-fold increase in HI titre post-vaccination.

Secondary outcomes

• Immunogenicity - Percentages of participants with seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart. [28 days post-administration of 2 doses of avian influenza A (H5N1)]: Definition of Seroconversion rate: the proportion of subjects who were either seronegative prior to vaccination and have a protective post-vaccination HI titre of ≥ 1:40 or who were seropositive prior to vaccination and have at least a 4-fold increase in HI titre post-vaccination) as acceptable by regulators for approval of a Pandemic influenza Vaccine (22). Definition of Geometric mean fold rise: the ratio of the post-vaccination geometric mean HI titre divided by the pre-vaccination geometric mean HI titre) acceptable by regulators for approval of a Pandemic influenza Vaccine (22).
• Immunogenicity - GMT of HI against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart. [28 days post-administration of 2 doses of avian influenza A (H5N1) vaccine]: GMT of HI against the H5N1 2.3.4.4b clade 28 days following administration of 2 doses of avian influenza A(H5N1) vaccine given 3 vs. 8 weeks apart.
• Immunogenicity - Percentages of participants with seroprotection, seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade [at baseline, at 3 weeks, at 8 weeks, 12 weeks, 26 weeks and through study completion (average of 1 year).]: Percentages of participants with seroprotection, seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade following administration of 1 dose of avian influenza A(H5N1) vaccine.
• Immunogenicity - Percentages of participants with seroprotection, seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade [6 and 12 months after the first dose of avian influenza A (H5N1) vaccine]: Percentages of participants with seroprotection, seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade 6 and 12 months after the first dose of avian influenza A(H5N1) vaccine given 3 vs. 8 weeks apart.
• Incidence of Grade 3 & 4 Adverse Events [Up to 12 months after the first dose of avian influenza A (H5N1) vaccine]: The following AEFIs will be collected in all participants: 1. Grade 3 solicited local and systemic adverse events in the 7 days following vaccine receipt; 2. SAEs at any time after vaccine receipt during the study; 3. MAAE at any time after vaccine receipt during the study, 4. AESI at any time after vaccine receipt during the study; 5. Provincially reportable AEFI at after vaccine receipt; and 6. acceptability as measured by participant questionnaire. Solicited adverse events and grading Grade 3 and 4 solicited local (injection-site) and systemic adverse events occurring during the 7-day follow-up period after each injection will be recorded. Solicited local (injection-site) adverse events (Pain, redness and swelling at injection site). Solicited systemic AEs, grade 3 and 4 will be recorded (Fatigue, fever - recorded, headache, nausea, diarrhea, vomiting, generalized muscle aches, joint pain and chills).

Sex: All, ages: 18 Years to 59 Years, accepts healthy volunteers

Inclusion Criteria:

1. Individuals in stable health (defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination) 18-59 years of age.
2. Able to comply with the trial procedures.
3. Informed consent signed prior to trial-specific procedures.
4. If a person is at risk of becoming pregnant, has practiced adequate contraception for 28 days prior to visit 1, and has a negative pregnancy test on the day of vaccination and has agreed to continue adequate contraception until 60 days after the final vaccination.

Risk of pregnancy is defined as any cis woman and/or gender divergent individual assigned female at birth or with reproductive capacity who is sexually active with individuals with sperm-producing capabilities.

Individual who are post-menopausal or permanently sterile (hysterectomy, bilateral salpingectomy) are not considered at risk of pregnancy. A post-menopausal state is defined as a no menses for 12 months.

Effective contraception methods are:

* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

  * Oral
  * Intravaginal
  * Transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation:

  * Oral
  * Injectable
  * Implantable
* Intra-uterine device (IUD) with or without hormonal release.
* Vasectomised partner, provided that this partner is your sole sexual partner and that the vasectomised partner has received a medical assessment of the surgical success.
* Credible self-reported history of heterosexual abstinence prior to and for at least 28 days after the vaccine.

Effective contraception methods are:

* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

  * Oral
  * Intravaginal
  * Transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation:

  * Oral
  * Injectable
  * Implantable
* Intra-uterine device (IUD) with or without hormonal release.
* Vasectomised partner, provided that this partner is your sole sexual partner and that the vasectomised partner has received a medical assessment of the surgical success.
* Credible self-reported history of heterosexual abstinence prior to and for at least 28 days after the vaccine.

Exclusion Criteria:

* Any of the following:

  1. Receipt of avian influenza A(H5N1) vaccine anytime.
  2. Positive pregnancy test prior to vaccination, or breastfeeding.
  3. Receipt of immunoglobulins and/or any blood products within 3 months preceding the first dose of study vaccine and for one month after the last dose of study vaccine (except Rho D).
  4. Bleeding disorder or history of significant bleeding following IM injections or venipuncture.
  5. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia, or immunosuppressant medication within the past 6 months except short term oral steroids (≤14 days duration) or topical steroids.
  6. A significant acute disease or temperature ≥38 Co within 24 hours prior to vaccination (temporary exclusion criteria, participants can return for evaluation to be randomized/ vaccinated 72 hours after symptoms resolve).
  7. Unstable chronic medical condition requiring ongoing follow-up and monitoring by a physician as determined by the investigator.
  8. History of anaphylaxis or allergy to any of the constituents or trace residues of the study vaccine, including egg protein.
  9. Receipt of non-study vaccine(s) 2 weeks prior to the study vaccine or planned 2 weeks after administration of the study vaccine.

• Joanne M Langley, Principal investigator, CIRN, Canadian Center for Vaccinology, Dalhousie University