Safety & Immunogenicity of an Alternative Immunization Schedule of GSK Bio's Pandemic Influenza Vaccine (GSK1119711A)

• Serum anti-haemagglutinin (HA)antibody titers, in Group C [ Time Frame: At Day 0, Month 6, Month 6+ 7 Days, Month 6 + 21 Days ] [ Designated as safety issue: No ]
• Geometric mean titres (GMTs) of H5N1 antibody titers [ Time Frame: At Day 0, Month 6, Month 6+ 7 Days, Month 6+ 21 Days ] [ Designated as safety issue: No ]
• Seroconversion rates (SC) [ Time Frame: At Month 6, Month 6+ 7 Days, Month 6+ 21 Days ] [ Designated as safety issue: No ]
• Seroconversion factors [ Time Frame: At Month 6, Month 6+ 7 Days, Month 6+ 21 Days ] [ Designated as safety issue: No ]
• Seroprotection rates [ Time Frame: At Day 0, Month 6, Month 6+ 7 Days, Month 6+ 21 Days ] [ Designated as safety issue: No ]
• Occurence of solicited local and general signs and symptoms [ Time Frame: During a 7-day follow-up period after each vaccination and overall. ] [ Designated as safety issue: Yes ]
• Occurence of unsolicited local and general signs and symptoms [ Time Frame: During a 30-day follow-up period after priming vaccination(s) and booster vaccination, and overall. ] [ Designated as safety issue: Yes ]
• Occurrence of serious adverse events [ Time Frame: During the entire study. ] [ Designated as safety issue: Yes ]

• Humoral immune response at Month 6
• Safety during the entire study
• Reactogenicity for 30 days

• GMTs of anti-HA antibody titres [ Time Frame: At Day 0, Day 21, Day 42, Month 6/12, Month 6/12 + 7days, Month 6/12 + 21 days, Month 18 ] [ Designated as safety issue: No ]
• Seroconversion rates [ Time Frame: At Day 21, Day 42, Month 6/12, Month .6/12 + 7days, Month 6/12 + 21 days, Month 18. ] [ Designated as safety issue: No ]
• In addition, humoral immune response in terms of anti-HA antibodies: Seroconversion factors [ Time Frame: At Day 21, Day 42, Month 6/12, Month .6/12 + 7days, Month 6/12 + 21 days, Month 18 ] [ Designated as safety issue: No ]
• Seroprotection rates [ Time Frame: At Day 0, Day 21, Day 42, Month 6/12, Month .6/12 + 7days, Month 6/12 + 21 days, Month 18 ] [ Designated as safety issue: No ]
• Frequency of influenza-specific CD4/CD8 T-cells per 10E6 in tests producing at least two different cytokines [ Time Frame: At Day 0, Month 6/12, Month 6/12 + 7 Days, Month 6/12 + 21 Days and Month 18 ] [ Designated as safety issue: No ]
• Frequency of influenza-specific CD4/CD8 T-cells per 10E6 in tests producing at least CD40L and another signal molecule (IL-2, IFN-γ, TNF-α) [ Time Frame: At Day 0, Month 6/12, Month 6/12 + 7 Days, Month 6/12 + 21 Days and Month 18 ] [ Designated as safety issue: No ]
• Frequency of influenza-specific CD4/CD8 T-cells per 10E6 in tests producing at least IL-2 and another signal molecule (CD40L, IFN-γ, TNF-α) [ Time Frame: At Day 0, Month 6/12, Month 6/12 + 7 Days, Month 6/12 + 21 Days and Month 18 ] [ Designated as safety issue: No ]
• Frequency of influenza-specific CD4/CD8 T-cells per 10E6 in tests producing at least TNF-α and another signal molecule (IL-2, IFN-γ, CD40L) [ Time Frame: At Day 0, Month 6/12, Month 6/12 + 7 Days, Month 6/12 + 21 Days and Month 18 ] [ Designated as safety issue: No ]

• Humoral immune response up to Month 18
• Cellular immune response at 6, 12 and 18 months

The aim of the study is to assess the safety & immunogenicity of a pandemic influenza vaccine administered at 2 different time points. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

• Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
  2 or 3 doses, intramuscular injection, at different time points.
• Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 2
  2 or 3 doses, intramuscular injection, at different time points.

• Experimental: Group A
  Subjects received two doses of vaccine
  Intervention: Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
• Experimental: Group B
  Subjects received two doses of vaccine
  Intervention: Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
• Experimental: Group C
  Subjects received two doses of vaccine
  Interventions:

  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 2
• Experimental: Group D
  Subjects received two doses of vaccine
  Interventions:

  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 2
• Experimental: Group E
  Subjects received three doses of vaccine
  Intervention: Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
• Experimental: Group F
  Subjects received three doses of vaccine
  Intervention: Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
• Experimental: Group G
  Subjects received three doses of vaccine
  Interventions:

  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 2
• Experimental: Group H
  Subjects received three doses of vaccine
  Interventions:

  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 1
  • Biological: Pandemic influenza vaccine (GSK1119711A)-formulation 2

• Schwarz TF et al. AS03-adjuvanted pre-pandemic H5N1 vaccines in a randomized trial: Single dose Clade 1 strain primary vaccination enables a strong, broad and rapid immune response to Clade 2 strain booster vaccination in adults. Abstract presented at the 3rd International Conference on Influenza Vaccines for the World (IVW), Cannes, France, 27-30 April 2009.
• Schwarz TF, Horacek T, Knuf M, Damman HG, Roman F, Dramé M, Gillard P, Jilg W. Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults. Vaccine. 2009 Oct 23;27(45):6284-90.
• Roman F et al. AS03 adjuvant system prepares the immune system for a fast and strong immune response after vaccination with a heterologous H5N1 influenza vaccine. Abstract presented at the 3rd Vaccine Global Congress, Singapore, Singapore, 4-6 October 2009.
• Gillard P, Caplanusi A, Knuf M, Roman F, Walravens K, Moris P, Dramé M, Schwarz TF. An assessment of prime-boost vaccination schedules with AS03A -adjuvanted prepandemic H5N1 vaccines: a randomized study in European adults. Influenza Other Respi Viruses. 2013 Jan;7(1):55-65. doi: 10.1111/j.1750-2659.2012.00349.x. Epub 2012 Mar 9.

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female between, and including, 18 and 60 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to first vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

• Administration of licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study.
• History of vaccination with investigational influenza pandemic vaccine.
• History of administration of an experimental/licensed vaccine
• Planned administration of a vaccine not foreseen by the study protocol during the following periods: from Day 0 up to Day 51; from 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Month 6 and Month 12; from Month 6 up to Month 6 + 30 days; from Month 12 up to Month 12 + 30 days.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first administration of the candidate vaccines
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
• History of hypersensitivity to vaccines.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• History of chronic alcohol consumption and/or drug abuse.
• Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the candidate vaccine or during the study.
• Lactating women.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period.
• Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.