Safety and Immunogenicity of GSK Biologicals' Malaria Vaccine 257049 When Administered on 7 Schedules to African Infants

• Occurrence of SAEs [ Time Frame: From study start until Month 10 ] [ Designated as safety issue: No ]
• Anti-Circumsporozoite protein of P. falciparum antibody titers [ Time Frame: At 1 month post last dose of the experimental malaria vaccine ] [ Designated as safety issue: No ]

• Occurrence of unsolicited symptoms [ Time Frame: After each vaccine administration over a 30 day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of solicited general and local reactions [ Time Frame: After each vaccine administration over a 7 day follow-up period (day of vaccination and 6 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of parameters of haematological (white blood cells, platelet and hemoglobin) and biochemical (creatinine and alanine aminotransferase) monitoring according to a toxicity grading scale. [ Time Frame: At screening,Day6 postdose1&1mth postdose3 for all groups except:10,14,26group:at screening,Day6 postdose1 of DTPw HepB Hib,Day6 postdose1,1 mth postdose3.Control&HB group: at screening,Day6 postdose of OPV & BCG &1mth postdose3 of DTPw HepB Hib, Mth7&10 ] [ Designated as safety issue: No ]
• Anti-CS antibody titers [ Time Frame: At screening,1mth postdose2,1mth postdose3,Mth10 and 18 for all groups except: 14,26,9M group: at screening,1mth postdose2,1mth postdose3 & Mth18.Control&HB group: at screening,1mth postdose2 of DTPw HepB Hib,1month postdose3 of DTPw HepB Hib, Mth7,10&18 ] [ Designated as safety issue: No ]
• Anti-HBs antibody titers [ Time Frame: At screening,1month postdose 3,Month 10 and 18 for all groups except: 14, 26, 9M group: at screening,1month postdose 3 and Month 18.Control & HB group: at screening,1month postdose 3 of DTPw HepB Hib,Month 7, 10 and 18. ] [ Designated as safety issue: No ]
• Anti-diphtheria antibody titers [ Time Frame: At month 5 (all groups) ] [ Designated as safety issue: No ]
• Anti-tetanus antibody titers [ Time Frame: At month 5 (all groups) ] [ Designated as safety issue: No ]
• Anti-PRP antibody titers [ Time Frame: At month 5 (all groups) ] [ Designated as safety issue: No ]
• Anti-polio types 1, 2 and 3 antibody titers [ Time Frame: At month 5 (all groups) ] [ Designated as safety issue: No ]
• Anti-BPT antibody titers [ Time Frame: At month 5 (all groups) ] [ Designated as safety issue: No ]
• Anti-measles antibody titers [ Time Frame: At month 10 (for 14,26, 9M and Control and HB groups) ] [ Designated as safety issue: No ]

• Occurrence of unsolicited symptoms [ Time Frame: After each vaccine administration over a 30 day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of solicited general and local reactions [ Time Frame: After each vaccine administration over a 7 day follow-up period (day of vaccination and 6 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of parameters of haematological (white blood cells, platelet and hemoglobin) and biochemical (creatinine and alanine aminotransferase) monitoring according to a toxicity grading scale. [ Time Frame: At screening,Day 6 postdose 1&1mth postdose3 for all groups except: 10,14,26group: at screening,Day 6 postdose1 of DTPw HepB Hib,Day 6 postdose1,1 mth postdose3.Control&HB group: at screening,Day 6 postdoses of OPV & BCG &1mth postdose3 of DTPw HepB Hib ] [ Designated as safety issue: No ]
• Anti-CS antibody titers [ Time Frame: At screening,1mth postdose2,1mth postdose3,Mth10 and 18 for all groups except: 14,26,9M group: at screening,1mth postdose2,1mth postdose3 & Mth18.Control&HB group: at screening,1mth postdose2 of DTPw HepB Hib,1month postdose3 of DTPw HepB Hib, Mth7,10&18 ] [ Designated as safety issue: No ]
• Anti-HBs antibody titers [ Time Frame: At screening,1month postdose 3,Month 10 and 18 for all groups except: 14, 26, 9M group: at screening,1month postdose 3 and Month 18.Control & HB group: at screening,1month postdose 3,Month 7, 10 and 18 ] [ Designated as safety issue: No ]
• Anti-diphtheria antibody titers [ Time Frame: At Month 5 ] [ Designated as safety issue: No ]
• Anti-tetanus antibody titers [ Time Frame: At Month 5 ] [ Designated as safety issue: No ]
• Anti-PRP antibody titers [ Time Frame: At Month 5 ] [ Designated as safety issue: No ]
• Anti-polio types 1, 2 and 3 antibody titers [ Time Frame: At Month 5 ] [ Designated as safety issue: No ]
• Anti-BPT antibody titers [ Time Frame: At Month 5 ] [ Designated as safety issue: No ]

The aim of the malaria vaccine program of the MVI/GSK partnership is to develop an efficacious malaria vaccine that is deliverable through the existing system, the Expanded Program on Immunization (EPI) of WHO. This study has been designed to:

• Investigate the safety and immunogenicity of 7 infant immunization schedules of the experimental malaria vaccine integrated with an EPI regimen.
• Investigate how to maximize the antibody response to the experimental malaria vaccine.

• Biological: GSK Biological's Investigational Malaria Vaccine 257049
  3 doses, IM route: left antero-lateral thigh administered in: Group <= 7d, 10 , 14 at less than 7 days, at 10 and 14 weeks of age Group <= 7d, 10, 26 at less than 7 days, at 10 and 26 weeks of age Group 6, 10, 14 at 6, 10 and 14 weeks of age Group 6, 10, 26 at 6, 10 and 26 weeks of age Group 6, 10, 26 &amp; HB at 6, 10 and 26 weeks of age Group 10, 14, 26 at 10, 14 and 26 weeks of age Group 14, 26, 9M at 14 and 26 weeks of age and at 9 months of age
• Biological: EngerixTM-B
  1 dose, IM route: left antero-lateral thigh at birth
• Biological: Tritanrix™ HepB Hib
  3 doses, IM route: right antero-lateral thigh at 6, 10 and 14 weeks of age
• Biological: BCG
  1 dose, intradermal route: shoulder at birth
• Biological: OPV
  4 doses, oral, at birth and at 6, 10 and 14 weeks of age
• Biological: Rouvax
  1 dose, IM route: right antero-lateral thigh at 9 months of age

• Experimental: Group <= 7d, 10, 14

  Children enrolled to this group will receive 3 doses of the experimental malaria vaccine at less than or equal to 7 days, 10 weeks and 14 weeks of age. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Experimental: Group <= 7d, 10, 26

  Children enrolled to this group will receive 3 doses of experimental malaria vaccine at less than or equal to 7 days, 10 weeks and 26 weeks of age. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Experimental: Group 6, 10, 14

  Children enrolled to this group will receive 3 doses of experimental malaria vaccine at 6, 10 and 14 weeks of age. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Experimental: Group 6, 10, 26

  Children enrolled to this group will receive 3 doses of experimental malaria vaccine at 6, 10 and 26 weeks of age. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Experimental: Group 6, 10, 26 & HB

  Children enrolled to this group will receive 3 doses of the experimental malaria vaccine at 6, 10 and 26 weeks of age with a neonatal dose of Hepatitis B vaccine at birth. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: EngerixTM-B
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Experimental: Group 10, 14, 26

  Children enrolled to this group will receive 3 doses of experimental malaria vaccine at 10, 14 and 26 weeks of age. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Experimental: Group 14, 26, 9M

  Children enrolled to this group will receive 3 doses of experimental malaria vaccine at 14, 26 weeks and 9 months of age. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: GSK Biological's Investigational Malaria Vaccine 257049
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax
• Active Comparator: Group control & HB

  Children enrolled to this group will receive a neonatal dose of Hepatitis B vaccine at birth. They will also be administered the EPI vaccines

  • BCG at birth (BCG),
  • DTPw/HepB-Hib at 6, 10 and 14 weeks of age
  • OPV at birth, 6, 10 and 14 weeks of age
  • measles at 9 months of age
  Interventions:

  • Biological: EngerixTM-B
  • Biological: Tritanrix™ HepB Hib
  • Biological: BCG
  • Biological: OPV
  • Biological: Rouvax

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

• A male or female infant between 1 and 7 days (inclusive) of age (where day 1 is day of birth).
• Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.
• Born to a mother negative for HIV antibody and Hepatitis B surface antigen.
• Subjects who are born after a normal gestation period (between 37 and 42 weeks) (Gestational age will be determined by carrying out a clinical assessment on infants according to the principles set out by Dubowitz (1970) in the first 5 days of life).
• A minimum weight of 2.5 kg.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

• Acute or chronic illness determined by clinical or physical examination and laboratory screening tests including, but not limited to:

  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • A family history of congenital or hereditary immunodeficiency.
  • Major congenital defects.
  • History of any neurological disorders or seizures.
• Laboratory screening tests out of normal ranges/limits defined per protocol.
• Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b, hepatitis B, BCG tuberculosis, measles or oral polio vaccines.
• Planned administration/administration of a licensed vaccine (i.e. a vaccine that is approved by one of the following authorities: FDA or EU member state or WHO [with respect to prequalification]) not foreseen by the study protocol within 7 days of the first dose of study vaccine.
• Administration of immunoglobulins, blood transfusions or other blood products since birth to the first dose of study vaccine or planned administration during the study period.
• Use of a drug or vaccine that is not approved for that indication (by one of the following authorities: FDA or EU member state or WHO [with respect to prequalification]) other than the study vaccine starting at birth or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• Simultaneous participation in any other clinical trial.
• Same-sex twins (to avoid misidentification).
• Maternal death.
• History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Children will not be enrolled if any maternal, obstetrical or neonatal event that has occurred might, in the judgment of the investigator, result in increased neonatal/infant morbidity
• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.