Neonatal Immunization With Pneumococcal Conjugate Vaccine in Papua New Guinea

Study Overview
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Brief Summary
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The National Health Plan 2001-2010 calls for investigation of the feasibility of pneumococcal vaccines for Papau New Guinea. The Papua New Guinea (PNG) Institute of Medical Research, the Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia will collaborate to examine very closely the safety of neonatal vaccination, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries.

Detailed Description
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In order to obtain the earliest possible protection against invasive pneumococcal disease, achieve optimal coverage and reduce burden of early carriage, neonatal pneumococcal conjugate vaccine (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 (infant schedule according to PNG national EPI schedule) or 0-1-2 months of age (neonatal schedule) or receive only routine immunizations (controls). Blood samples will be taken at birth-2-3-4 months of age, pre- and post-pneumococcal polysaccharide booster (23vPPV) 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 pneumococcal 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.

Official Title
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Neonatal Immunization With Pneumococcal Conjugate Vaccine in Papua New Guinea

Conditions
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Pneumonia, Meningitis, Otitis Media

Intervention / Treatment
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* Biological: Pneumococcal 7 valent conjugate vaccine (Prevenar®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New born babies with birth weight >2000 g (2 kgs) and parents giving consent Exclusion Criteria: Acute neonatal infection; Severe congenital abnormality; Children of mothers known to be HIV positive will be excluded; Serious asphyxia at birth; Intended migration in the next 2 years; Parents withdraw consent;

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neonatal 7vPCV<br>Receive study vaccine (Prevnar) at birth, 1 and 2 months | Biological: Pneumococcal 7 valent conjugate vaccine (Prevenar®)<br>* Accelerated PCV vaccinaton.<br>|
| Experimental: Infant 7vPCV<br>Receive the study vaccine (Prevnar) at 1, 2 and 3 months | Biological: Pneumococcal 7 valent conjugate vaccine (Prevenar®)<br>* Accelerated PCV vaccinaton.<br>|
| Placebo Comparator: Control<br>Do not receive study vaccine (Prevnar) | Biological: Pneumococcal 7 valent conjugate vaccine (Prevenar®)<br>* Accelerated PCV vaccinaton.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity and Safety | Serum PCV serotype-specific IgG antibody at 2, 4 and 9 mths. Mucosal PCV serotype-specific IgG antibody at 1, 3, 4 and 9 mths. PCV-induced T-cell memory (against vaccine protein carrier) at 3 and 9 mths. Local and systemic reactogenicity 48-96 hrs after vaccination. Monitoring of serious adverse events during 18 mth follow-up. T-cell development to bystander antigens at 3 and 9 mths. | 5 yrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Serum PCV and non-PCV serotype specific IgG antibody at 10 mths, after 23vPPV vaccination at 9 mths | 5 years | 
| Pneumococcal-specific acquired immunity | Assessment of cellular immune responses to pneumococcal protein antigens at 9 and 18 months of age. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal vaccine, Antibody responses, Cellular immunology, Th1/Th2 immune responses, Paediatric, Neonatal, Infectious diseases, Papua New Guinea