Pneumococcal Conjugate Vaccine Followup (PCVFU)

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

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.

Study Overview

• Status: Completed
• Conditions: Immune Tolerance
• Intervention / Treatment: Biological: Prevenar + PPV; Biological: Infant PCV (Prevenar) + PPV at 9 months; Biological: No Prevenar + PPV at 9 months; Biological: Control

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 2

Contacts and Locations

Study Locations

• Papua New Guinea
  • Eastern Highlands
    • Goroka, Eastern Highlands, Papua New Guinea, 441
      • PNG Institute of Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: William Pomat
• Collaborators: The University of Western Australia
• Investigators: Principal Investigator: Peter C Richmond, MD, School of Paediatrics and Child Health, University of Western Australia; Principal Investigator: Deborah Lehmann, MSc, Telethon Institute for Child Health Research; Principal Investigator: William S Pomat, PhD, Papua New Guinea Institute of Medical Research

Publications and helpful links

General Publications

• van den Biggelaar AHJ, Richmond PC, Fuery A, Anderson D, Opa C, Saleu G, Lai M, Francis JP, Alpers MP, Pomat WS, Lehmann D. Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination. PLoS One. 2017 Oct 13;12(10):e0185877. doi: 10.1371/journal.pone.0185877. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 2, 2011
• First Submitted That Met QC Criteria: August 10, 2011
• First Posted (Estimate): August 11, 2011

Study Record Updates

• Last Update Posted (Estimate): September 17, 2012
• Last Update Submitted That Met QC Criteria: September 14, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: pneumococcal,; pneumococcal polysaccharide vaccine,; challenge dose,; hyporesponsiveness,; Papua New Guinea
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: PCVFU927