PAPI (Splenectomy)

Protecting asplenic children and adults against pneumococcal disease and identifying optimal immunisation regimens. A Phase IV, multicentre, randomised study to compare the safety, tolerability and immunogenicity of pneumococcal immunisation regimens in patients with asplenia.

Intervention(s)
Asplenic adults and children aged over 10 years will be administered a licensed pneumococcal 10 valent conjugate vaccine (Synflorix). This is a 10 valent polysaccharide-protein conjugate vaccine containing saccharides of the capsular antigen of Streptococcus pneumoniae (pneumococcus) serotypes 1,4, 5 6B, 7F, 9V, 14, 18C, 19F and 23F individually conjugated to protein D (PD) carrier protein derived from Non-typable Haemophilus inlfuenzae, serotype 18C conjugated to tetanus toxoid (TT) carrier protein, and 19F conjugated to diphtheria toxoid (DT) carrier protein. It will be given once to patients in 3 arms of the study and omitted from the 4th arm (they will have pneumococcal polysaccharide vaccine only).

Objectives
Primary
1(a) To describe the serotype specific immune response in Streptococcus pneumoniae (SP) polysaccharide vaccine (PPV23) naïve and experienced hyposplenic adults and children >10 years ofage 6 weeks following Streptococcus pneumoniae SP conjugate vaccine (PCV10) as measured by quantitative ELISA geometric mean titre (GMT)

1(b) To describe the functional serotype specific immune response in SP polysaccharide (PPV23) vaccine naïve and experienced hyposplenic adults and children >10 years of age 6 weeks following Streptococcus pneumoniae SP conjugate vaccine (PCV10) as measured by the opsonophagocytic assay (OPA) geometric mean titre (GMT)

2(a) To compare the quantitative serotype specific immune response as measured by the ELISA GMC 6 weeks after receiving a first dose of PPV23 performed 6 weeks (early) or 6 months (late) after PCV10 vaccination in adults and children who have not previously been exposed to PPV23 vaccine

2(b) To compare the functional serotype specific immune response 6 weeks as measured by the OPA GMT after receiving a first dose of PPV23 performed 6 weeks (early) or 6 months (late) after PCV10 vaccination in adults and children who have not previously been exposed to PPV23 vaccine

3 In PPV23 experienced hyposplenic adults and children, describe the immune persistence prior to revaccination with PCV10 or PPV23 of serotype specific antibodies against 10 serotypes contained in PPV23 prior to revaccination, measured by ELISA.

4(a) In PPV23 experienced hyposplenic adults and children compare quantitative serotype specific ELISA immune responses to (a) PCV10 followed by PPV23, with (b) PPV23, measured 6 weeks following PPV23

4(b) In PPV23 experienced hyposplenic adults and children compare functional serotype specific OPA immune responses to (a) PCV10 followed by PPV23, with (b) PPV23, measured 6 weeks following PPV23

Secondary
1. Describe the frequency of local reactions following PPV23 according to the number of previous doses received.
2. Describe the reactogenicity and safety of PCV10 in hyposplenic adults and children >10 years of age

Sponsor(s)
NHMRC
MCRI