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Evaluation of different infant vaccination schedules incorporating pneumococcal vaccination (The Vietnam Pneumococcal Project): protocol of a randomised controlled trial
  1. Beth Temple1,2,3,
  2. Nguyen Trong Toan4,
  3. Doan Y Uyen4,
  4. Anne Balloch3,
  5. Kathryn Bright3,
  6. Yin Bun Cheung5,6,
  7. Paul Licciardi3,7,
  8. Cattram Duong Nguyen3,7,
  9. Nguyen Thi Minh Phuong4,
  10. Catherine Satzke3,7,
  11. Heidi Smith-Vaughan8,
  12. Thi Que Huong Vu9,
  13. Tran Ngoc Huu4,
  14. Edward Kim Mulholland2,3
  1. 1 Global Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
  2. 2 Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
  3. 3 Pneumococcal Research, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
  4. 4 Department of Disease Control and Prevention, Pasteur Institute of Ho Chi Minh City, Ho Chi Minh City, Viet Nam
  5. 5 Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore
  6. 6 Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
  7. 7 Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  8. 8 Child Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
  9. 9 Microbiology and Immunology, Pasteur Institute of Ho Chi Minh City, Ho Chi Minh City, Viet Nam
  1. Correspondence to Beth Temple; beth.temple{at}menzies.edu.au
  • TQHV is deceased.

Abstract

Introduction WHO recommends the use of pneumococcal conjugate vaccine (PCV) as a priority. However, there are many countries yet to introduce PCV, especially in Asia. This trial aims to evaluate different PCV schedules and to provide a head-to-head comparison of PCV10 and PCV13 in order to generate evidence to assist with decisions regarding PCV introduction. Schedules will be compared in relation to their immunogenicity and impact on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.

Methods and analysis This randomised, single-blind controlled trial involves 1200 infants recruited at 2 months of age to one of six infant PCV schedules: PCV10 in a 3+1, 3+0, 2+1 or two-dose schedule; PCV13 in a 2+1 schedule; and controls that receive two doses of PCV10 and 18 and 24 months. An additional control group of 200 children is recruited at 18 months that receive one dose of PCV10 at 24 months. All participants are followed up until 24 months of age. The primary outcome is the post-primary series immunogenicity, expressed as the proportions of participants with serotype-specific antibody levels ≥0.35 µg/mL for each serotype in PCV10.

Ethics and dissemination Ethical approval has been obtained from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (EC00153) and the Vietnam Ministry of Health Ethics Committee. The results, interpretation and conclusions will be presented to parents and guardians, at national and international conferences, and published in peer-reviewed open access journals.

Trial registration number NCT01953510; Pre-results.

  • Clinical Trials
  • Microbiology
  • Epidemiology

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Contributors BT was involved with the study design, led the funding and ethics applications, has been involved in the day-to-day management of the trial and data analysis, and drafted the protocol and this manuscript. NTT advised on the study design and location, was involved in the approval processes in Vietnam and has been involved in the day-to-day management and implementation of the trial. DYU advised on the study design and location and has been involved in the day-to-day implementation of the trial. AB advised on the study design, assisted with the funding applications, and advised on and provided oversight of the immunology laboratory procedures. KB advised on the study design and location and has been responsible for the day-to-day management and implementation of the trial. YBC advised on the study design and funding applications, especially the statistical aspects of the trial. PL advised on the study design, assisted with the funding applications, and advised on and provided oversight of the immunology laboratory procedures. CDN advised on the study design and statistical analysis plan. NTMP advised on the study design and location, was involved in the approval processes in Vietnam and has been involved in the day-to-day management of the trial. CS advised on the study design, assisted with the funding applications, and advised on and provided oversight of the microbiology laboratory procedures. HS-V advised on the study design, assisted with the funding applications, and advised on and provided oversight of the microbiology laboratory procedures. TQHV advised on the study design and advised on and provided oversight of the laboratory procedures at Pasteur. TNH advised on the study design and location, undertook consultations, was involved in the approval processes in Vietnam and has had overall responsibility for the conduct of the trial in Vietnam as Site Principal Investigator. EKM conceived the study, undertook consultations, provided oversight for the funding and ethics applications, provided oversight for the conduct of the trial and data analysis, and has had overall responsibility for all aspects of the trial as the Principal Investigator. All authors contributed to refinement of the study protocol and reviewed and approved this manuscript.

  • Funding This work is supported by the National Health and Medical Research Council of Australia (grant no. 566792) and the Bill and Melinda Gates Foundation (grant no. OPP1116833). The doses of PCV10 and funding for the opsonophagocytic assays are provided by GlaxoSmithKline Biologicals SA (GSK).

  • Competing interests All authors receive salary support from grants from the National Health and Medical Research Council of Australia and/or the Bill and Melinda Gates Foundation. Non-financial support (in the form of PCV10 vaccine doses) and funding for opsonophagocytic assays are provided by GSK Biologicals SA. EKM is a member of the DSMB for a current Novavax trial, for which he receives consulting fees. He has received travel costs from the GSK group of companies for one international conference and an honorarium from Merck for one advisory group meeting. He does not have any paid consultancies with or receive any research funds from pharmaceutical companies. Members of CS’s team have received awards that were funded (but not assessed) by Pfizer. None of the authors have any other competing interests to declare.

  • Patient consent Guardian consent obtained.

  • Ethics approval Vietnam Ministry of Health Ethics Committee and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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