Pneumococcal Conjugate Vaccine Followup

Study Overview
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Brief Summary
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Recently, controversy has emerged regarding the role of the 23vPPV in infants due to potential immunological hypo-responsiveness (i.e. a poorer immune response to repeat vaccination). Although previous experience of 23vPPV in children in PNG has demonstrated protective efficacy against acute lower respiratory tract infection, the investigators feel it is a matter of urgency to determine if 23vPPV administration provides elevated antibody concentrations at 3 to 5 years of age, and to ensure the immunological safety of the 23vPPV in infants. Following consent and eligibility assessment, a baseline blood sample and nose swab will be taken, a 0.1ml dose of 23vPPV will be administered and a follow up blood sample and nose swab will be collected 28 days later. The investigators will also collect data on incidence of ALRI in all study participants by medical record review.

Official Title
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Pneumococcal Conjugate Vaccine Followup: Investigation of Serotype-specific Antibody Persistence and B Cell Memory at Age 3-5 Years Following 23valent Pneumococcal Polysaccharide Vaccine at Age 9 Months in PNG Children Previously Primed With 7valent Pneumococcal Conjugate Vaccine

Conditions
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Immune Tolerance

Intervention / Treatment
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* Biological: Prevenar + PPV
* Biological: Infant PCV (Prevenar) + PPV at 9 months
* Biological: No Prevenar + PPV at 9 months
* Biological: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PNG Infants aged 3 to 5 yrs of age who participated in previous PNG Neonatal PCV study and received PPV between 9 and 12 months of age, or age- and sex-matched controls who live in the same villages or urban area Informed parental/guardian consent Exclusion Criteria: Known HIV infection or other immunosuppressive condition or treatment. Prior receipt of 2 doses of pneumococcal polysaccharide vaccine

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 5 Years

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 |
| --- | --- |
| Active Comparator: Neonatal PCV + PPV 9 months<br>Group 1: Children receiving 7VPCV at 0-1-2 months of age and PPV at 9 months of age | Biological: Prevenar + PPV<br>* 0.5mL dose of Prevenar at 0-1-2 months, 0.5mL Pneumovax at 9 months and 0.1mL Pneumovax at 3-5 yrs<br>|
| Active Comparator: Infant PCV + PPV at 9 months<br>Group 2: Children receiving 7VPCV at 1-2-3 months of age and PPV at 9 months of age | Biological: Infant PCV (Prevenar) + PPV at 9 months<br>* 0.5mL Prevenar at 1-2-3 months,0.5mL Pneumovax (PPV) at 9 months, 0.1mL Pneumovax at 3-5 yrs<br>* Other names: Pneumovax23;|
| Active Comparator: No PCV + PPV at 9 months<br>Group 3: Children who only received PPV at 9 months of age | Biological: No Prevenar + PPV at 9 months<br>* no Prevenar, 0.5mL Pneumovax at 9 months, 0.1mL Pneumovax at 3-5 yrs<br>|
| Active Comparator: Control<br>Group 4: Children who have not received any previous pneumococcal vaccine | Biological: Control<br>* control, 0.1mL Pneumovax at 3-5yrs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure serotype-specific antibody persistence in children aged 3-5 years after vaccination with 23vPPV at 9 months of age and compared to unvaccinated controls. | Children who were previously vaccinated with Pneumovax (23vPPV) at 9 months will be followed up at age 3-5 years of age. They will be given a challenge dose of Pneumovax (0.1mL) and followed up 1 months later. Age matched controls identified from each villages will also be recruited and given a challenge dose of Pneumovax. Serotype-specific antibodies will be measure pre- and post-challenge dose to determine anitbody levels. | 2yrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the number of circulating serotype-specific memory B-cells pre- & post- booster immunisation |  | 2yrs | 
| Measure nasopharyngeal pneumococcal serotype-specific carriage rates pre- and post- 23vPPV challenge dose |  | 2yrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumococcal,, pneumococcal polysaccharide vaccine,, challenge dose,, hyporesponsiveness,, Papua New Guinea