Safety and Efficacy Study of Investigational Pneumococcal Vaccine in Elderly Population

• Occurrence, intensity and relationship of any solicited local and general signs and symptoms. [ Time Frame: During a 7-day follow up period after each vaccine dose. ] [ Designated as safety issue: No ]
• Occurrence, intensity and relationship to vaccination of unsolicited local and general signs and symptoms. [ Time Frame: During a 30-day follow up period after each vaccine dose. ] [ Designated as safety issue: No ]
• Occurrence of all serious adverse events (SAE). [ Time Frame: During the entire study period. ] [ Designated as safety issue: No ]
• Anti- PhtD antibody concentration [ Time Frame: One month after the first injection ] [ Designated as safety issue: No ]
• Anti-PhtD antibody concentration. [ Time Frame: One month after 2 injections ] [ Designated as safety issue: No ]

• mmune response
• safety and reactogenicity throughout the entire study

• Number and percentage of subjects with normal or abnormal values for biochemical assessments and for haematological analysis. [ Time Frame: At each scheduled time point (month 0, 1, 3, 12, 24 and 36). ] [ Designated as safety issue: No ]
• Anti- PhtD antibody concentration. [ Time Frame: At 12, 24 and 36 months after the first vaccination. ] [ Designated as safety issue: No ]
• Anti-PhtD antibody avidity. [ Time Frame: At month 0, 1 and 3. ] [ Designated as safety issue: No ]
• Evaluation of protection afforded by passive transfer of anti PhtD antibodies sera pooled from all individuals. [ Time Frame: At month 0, 1 and 3. ] [ Designated as safety issue: No ]
• Frequency of PhtD specific plasma cells generated by in vitro cultivated memory B-cells, in a subset of subjects. [ Time Frame: At month 0, 1, 3, 12. ] [ Designated as safety issue: No ]
• Frequency of CD4 and/or CD8 T cells that produce cytokines (IL-2, IL-4, IFNg, CD40L and/or GM-CSF, and TNFα), upon PhtD re-stimulation in vitro, to evaluate the T-cell response, in a subset of subjects. [ Time Frame: At month 0, 1, 3, 12. ] [ Designated as safety issue: No ]
• Anti-polysaccharide total IgG concentration in Group A for all vaccine pneumococcal serotypes [ Time Frame: At month 0, 1, 12, 24 and 36. ] [ Designated as safety issue: No ]
• Anti-PS antibody avidity for 5 serotypes in Group A. [ Time Frame: At month 0 and 1. ] [ Designated as safety issue: No ]
• Deposition of complement components on the surface of different bacterial strains 3 strains (GSK/CDC, OPA, isogenic TIGR4) of 5 serotypes in Group A. [ Time Frame: At month 0 and 1. ] [ Designated as safety issue: No ]
• Opsonophagocytic activity titres in Group A to all vaccine pneumococcal serotypes [ Time Frame: At month 0, 1 and 12. ] [ Designated as safety issue: No ]
• Frequency of PS-specific plasma cells generated by in vitro cultivated memory B-cells in Group A in a subset of subjects. [ Time Frame: At month 0 and month 1. ] [ Designated as safety issue: No ]

• safety based on hematological and biochemical parameters throughout the study
• immune response at 1 year, 2 years and 3 years.
• immune response to the control Pneumovax 23™ throughout the study

As the licensed Pneumovax 23™ vaccine is not always satisfactory in elderly subjects, the safety and the immune response of the new investigational pneumococcal protein vaccine is evaluated in healthy elderly population.

Since influenza vaccination is recommended in the age range of the study population, Fluarix™ (GlaxoSmithKline Biologicals) vaccine will be offered free of charge during the study period (for 3 consecutive years starting from September 2004), to be used by Investigators according to national vaccination schedule/practice.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

• Biological: Pneumococcal vaccine GSK513026
  Two-dose intramuscular injection. Five different formulations, each administered to one Group
• Biological: Pneumovax 23™
  Single dose intramuscular injection.

• Active Comparator: Group A
  Intervention: Biological: Pneumovax 23™
• Experimental: Group B
  Intervention: Biological: Pneumococcal vaccine GSK513026
• Experimental: Group C
  Intervention: Biological: Pneumococcal vaccine GSK513026
• Experimental: Group D
  Intervention: Biological: Pneumococcal vaccine GSK513026
• Experimental: Group E
  Intervention: Biological: Pneumococcal vaccine GSK513026
• Experimental: Group F
  Intervention: Biological: Pneumococcal vaccine GSK513026

Inclusion criteria

• Subjects who the investigator believes will comply with the requirements of the protocol
• A male or female ≥ 65 years at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion criteria

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Use of any anticoagulants.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 2 weeks of the first dose of vaccines.
• Previous vaccination against Streptococcus pneumoniae.
• Bacterial pneumonia within 3 years prior to 1st vaccination.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Current serious neurologic or mental disorders.
• Currently smoking > 25 cigarettes per day.
• Inflammatory processes such as known chronic active infections
• All malignancies (excluding non-melanic skin cancer) and lymphoproliferative disorders diagnosed or treated actively during the past 5 years.
• History of administration of an experimental vaccine containing MPL or QS21.
• Acute disease at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, at the discretion of the investigator.
• History of chronic alcohol consumption and/or intravenous drug abuse.