• Serum Pnc serotype-specific IgG antibody at 2 mths. Serum Pnc st-specific IgG and Diphtheria toxoid antibody at 4 mths. Serum Pnc st-specific IgG antibody at 10 mths after PPV at 9 mths. Systemic adverse events after neonatal immunisation
  

Infants in Papua New Guinea (PNG) are at extremely high risk for invasive pneumococcal (Pnc) disease. Similar to other high-risk populations, PNG infants have neonatal onset of dense respiratory tract Pnc colonisation, which may have long-term effects on the development of protective immunity. Pnc conjugate vaccines (PCV) that are efficacious in American and African infants need evaluation in this high-risk PNG population under the national accelerated 1-2-3 month schedule. In order to obtain the earliest possible protection against invasive disease, achieve optimal coverage and reduce burden of early carriage, neonatal PCV immunization needs to be considered.

This study in the PNG highlands will enrol 312 infants at birth, who will be randomised to receive PCV either at 1-2-3 months or 0-1-2 months of age or receive only routine immunizations (controls). Blood samples will be taken at birth-2-3-4 months of age, pre- and post-Pnc polysaccharide booster at 9-10 months of age (to assess immune memory) and at 18 months at study completion. Carriage will be assessed weekly for the first month of life and at regular intervals thereafter. There will be ongoing surveillance for respiratory and other diseases throughout the study. In addition to serotype-specific IgG, we will examine IgG avidity, IgG subclasses, mucosal IgA and T-cell cytokine responses to PCV and Pnc protein antigens. To ensure immunological safety, particularly for neonatal PCV, immune responses to concomitant vaccines and viral and environmental antigens will also be examined as well as overall T-cell maturation. This study will provide proof of principle of the safety and immunological feasibility of neonatal PCV immunization, which is essential before progression to larger-scale studies in high-risk populations. This study will also examine the effect of early carriage on the development of systemic and mucosal immunity to Pnc infections and the impact of early PCV on carriage. It will further our understanding of the basic immunological mechanisms underlying conjugate vaccine responses during the critical neonatal period, and provide insight into the interactions between the developing T cell system and vaccines, which occur in these infants against a background of intense microbial stimulation. These studies are crucial for the optimal use of current vaccines and the development of new vaccines, for Pnc and other pathogens. This project will bring together the necessary expertise, innovative methodology and laboratory facilities in PNG and Australia to conduct the study in order to reduce this major burden on child health.