Safety and Immunogenicity of 10-valent and 13-valent Pneumococcal Conjugate Vaccines in Papua New Guinean Children (PCV1103)

• Proportion of children with serotype-specific IgG concentration >= 0.35ug/ml at 4 and 9 months of age for 90% of PCV vaccine serotypes and proportion of children with OPA >=1:8 titres at 4, 10 and 24 months [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  IgG concentration to vaccine serotypes are >= 0.35ug/ml post-dose 3 at 4 and 9 months. Serotype-specific IgG concentration >=0.35ug/ml is protective level against invasive pneumococcal diseases. Opsonophagocytic titre of >=1:8 examined at 4, 10 and 24 months will inform on functional antibodies induced by vaccination.
  
  

• Compare antibody concentrations to pneumococcal and Haemophilus influenzae protein antigens. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Measure antibody titres to surface proteins of pneumococci and Hi including Hi protein D, the carrier protein in PCV10 (Synflorix).
  
  
• Determine carriage rates and bacterial load of pneumococci and H.influenzae [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  Proportion of carriage before and after vaccination will be measured using conventional culture methods. Bacterial load will be measured using PCR to determine impact of vaccines
  
  
• Determine rates of hospital admission for acute respiratory tract infections at 9 and 23 months [ Time Frame: 2 yrs ] [ Designated as safety issue: Yes ]
  Admissions and morbidity for acute respiratory tract infections will be documented at 9 and 23 months.
  
  

The primary aim of the study is to determine whether PCV10 and PCV13 are safe and immunogenic in PNG infants for the serotypes in the respective vaccines. This study is important for the following reasons:

1. There is a lack of data worldwide on immunogenicity in populations with very high early onset of dense URT carriage.
2. The EPI immunisation schedule is very accelerated in PNG (ages 1,2 and 3 months).
3. There are not data on functional antibody to PCVs in PNG.
4. There are no data on NTHi Protein D antibody responses in PNG and worldwide in population with very high URT carriage rates from a young age, i.e. those most likely to benefit from a vaccine including NTHi protein carrier.
5. It is important to investigate impact of vaccine on carriage density in view of our finding of limited impact of 7vPCV on URT carriage.
6. There is no data on antibody responses following 10v or 13v PCV to booster with PPV as young as 9 months of age (which would be the most appropriate within the current PNG EPI schedule and in the many other third world countries).
7. There is no data on antibody responses (including functional assays) to 23vPPV challenge at age 2 years after 23vPPV booster at age 9 months in children primed with PCV.
8. The broad range of serotypes causing IPD in PNG necessitates continuing consideration of 23vPPV as a potential booster at age 9 months.
9. Serotype-specific B cell memory is an important aspect that we can now test to address immunological safety of PPV in children primed with PCV.
10. The Global Alliance for Vaccines and Immunisation (GAVI) and the World Health Organisation (WHO) have committed to the introduction of PCV for infants in GAVI-eligible countries (including PNG) using novel funding mechanism. In PNG, the introduction of a PCV is planned for 2013.