Immunization, Vaccines and Biologicals

Reconvened SAGE Working Group on Dengue Vaccines and Vaccination (December 2017 to October 2018)

Terms of Reference

The reconvened Dengue Working Group is asked to review new data on the long-term follow-up of dengue vaccine recipients. This includes data generated by further laboratory testing and analysis related to the long-term safety and efficacy of CYD-TDV Phase 3 trial participants. In particular, the group is asked to review the differential performance of the CYD-TDV vaccine (also known as Dengvaxia®) in subjects seronegative versus seropositive at the time of vaccination. The group is asked to advise on a revision of WHO’s current vaccine recommendations as published in July 2016. The review at SAGE is tentatively scheduled for April 2018. This will lead to the publication of an amended WHO position paper on the use of a dengue vaccine, which will replace the interim recommendation issued by WHO on 22 Dec 2017 (WHO interim position on the use of Dengvaxia®)

WHO interim position on the use of Dengvaxia®

The Working Group will specifically be asked to review data relating to:

  • the long-term safety, efficacy, immunogenicity profile and benefit/risk assessment of Dengvaxia stratified by serostatus
  • the schedule, age of administration, and potential vaccination strategies for targeting vaccination to individuals seropositive to dengue at the time of vaccination
  • the disease impact of dengue immunization programs identification of key data gaps and additional critical issues that need to be considered in drafting amended recommendations to SAGE

Composition

The working group is composed of its previous members, and additional ad hoc experts in accordance to the terms of reference

SAGE members

  • Terry Nolan, (Co-Chair of the Working Group), Melbourne School of Population and Global Health, Australia
  • Kate O`Brien (Member of the Working Group), Johns Hopkins International Vaccine Access Center (IVAC), Baltimore, USA

Experts

  • Jeremy Farrar, (Co-Chair of the Working Group), Wellcome Trust, UK
  • Piyanit Tharmaphornpilas, Ministry of Public Health, Thailand
  • Alan Barrett, University of Texas Medical Branch, USA
  • Elizabeth Ferdinand, University of the West Indies, Barbados
  • Maria Guzman, Pedro Kouri Tropical Medicine Institute, Cuba
  • Maria Novaes, Universidade de São Paulo, Brazil
  • Lee Ching Ng, National Environment Agency, Singapore
  • Peter Smith, London School of Hygiene and Tropical Medicine, UK

Ad hoc experts

  • Stefan Flasche, London School of Hygiene and Tropical Medicine, UK
  • In-Kyu Yoon, International Vaccine Institute, South Korea

WHO secretariat

  • Annelies Wilder-Smith
  • Joachim Hombach

Declaration of interests

All members completed a declaration of interest. Six members reported any relevant interests. It was concluded that all members could take part in full in all of the discussions. The reported relevant interests are summarized below:

Terence Nolan
  • He received consultancy fees for participating in meetings and for data analysis and interpretation as member of Data and Safety Monitoring Board (DSMB) and Independent Data Monitoring Committee (IDMC) on Human Papilloma Virus vaccine from GSK. The consultancy was ceased by the 17th October 2012. This interest was assessed as personal, non-specific and financially significant*.
  • In the time from 2008-2012 his institution received research support for vaccine trials implemented in Australia from a number of companies (including GSK, Wyeth, Novartis Vaccines, Sanofi Pasteur and CSL Ltd).These trials concern a number of vaccines (MenACWY, MenB, MenC, HibMenC Adult and peadiatric TIV, H1N1 and H5N1 vaccine and DTPa-Hib-hepB-IPV-MenC vaccine). This interest was assessed as non-personal, non-specific and financially significant*.
  • His institution receives research support to conduct a follow-up clinical trial on a birthdose of Pertussis Vaccination from GSK. This interest was assessed as non-personal, non-specific and financially significant*.
  • His institution receives research support to conduct a Meningococcal ACWY vaccine clinical trial from GSK. This interest was assessed as non-personal, non-specific and financially significant*.
  • He serves as principal investigator for a clinical trial assessing the antibody response and persistence following MenACWY-TT funded by GSK and Murdoch Childrens Research Institute. This interest was assessed as personal, non-specific and financially significant*.
Kate O`Brien
  • Serves as technical expert consultant for Astellas Pharma, Sutrovax, Merck, ClearPath, Affinivax and PATH on pneumococcal vaccination. This interest was assessed as non-personal, specific and financially insignificant*.
  • Serves as technical expert consultant for Sanofi Pasteur on RSV. This interest was assessed as non-personal, non-specific and financially insignificant*.
  • Served as member of DSMB on malaria RTS,S vaccine funded by PATH-Malaria Vaccine Initiative. This ceased in 2014. This interest was assessed as non-personal, non-specific and financially significant*.
  • Received funding for travel costs for a GSK Grand Convergence Meeting in 2015. This interest was assessed as non-personal, non-specific and financially insignificant*.
  • Her institution currently receives research grants from GSK, Gavi, JSI Research & Training Institute, Inc., BMGF, Pfizer and Yale regarding pneumococcal, rotavirus vaccines, biomarkers of vaccination status, vaccine coverage, programmatic impact of multi-dose vaccines, vaccine demand support, PCV impact evaluation and/or pneumonia etiology. This interest was assessed as personal, specific and financially significant*.
  • Her institution receives research grants from the National Institutes of Health (NIH) regarding pneumococcal epidemiology and vaccines. This interest was assessed as personal, specific and financially significant*.
  • Her institution received research grants from Merck on adult vaccines until June 2016. This interest was assessed as non-personal, non-specific and financially significant*.
  • Her institution received research grants from BMGF regarding a disease surveillance, country support of pneumococcal and rotavirus vaccines, vaccine demand approaches, technical country support and decision making on pneumococcal/rotavirus vaccine, PCV policy optimization and pneumcooccal, Hib and meningococcus etiology work (disease burden estimates). This interest was assessed as personal, specific and financially significant*.
  • Her institution received research grants from Gavi regarding scientific communication support and PCV product assessment. This interest was assessed as personal, specific and financially significant*.
  • Her institution received research grants from the Pfizer Foundation regarding monitoring of routine immunization coverage in Pakistan. This interest was assessed as personal, non-specific and financially significant*.
Piyanit Tharmaphornpilas
  • She received in 2011 a travel grant from a joint venture of the Thai Government Pharmaceutical Organization - Merieux Biological Product to attend the Re-invigorating Immunization Policy Implementation and Success: From Parent to Partner and from Broad to Engagement. This interest was assessed as personal, non-specific and financially significant*.
Peter Smith
  • He is a member of the Independent Data Monitoring Committee for Sanofi Pasteur’s dengue vaccine clinical trials. This interest was assessed as personal, specific, and financially significant*.
In-Kyu Yoon
  • His institution receives unrestricted grants from Sanofi Pasteur and other vaccine companies. This interest was assessed as non-personal, non-specific and financially significant*.
  • He served once on a Scientific Advisory Board for Merck on dengue vaccines. This interest was assessed as personal, non-specific, and financially non-signfiicant*.
Alan Barrett
  • His institution holds a contract funded by the U.S. National Institutes of Health to conduct a phase I clinical trial of the Takeda dengue vaccine candidate. This interest was assessed as non-personal, specific, and financially significant*.
  • His institution holds a contract funded by Merck to conduct a phase I clinical trial of the Merck dengue vaccine candidate. This interest was assessed as non-personal, specific, and financially significant*
  • His institution participates in collaborative projects with Hawaii Biotech/Merck, two of which study recombinant flavivirus immunogens (tick-borne encephalitis). This interest was assessed as non-personal, non-specific, and financially significant*.
  • He is co-investigator of a contract funded by the U.S. National Institutes of Health to test dengue drugs and vaccines in mouse models. This interest was assessed as personal, specific, and financially significant*.

* According to WHO's Guidelines for Declaration of Interests (WHO expert), an interest is considered "personal" if it generates financial or non-financial gain to the expert, such as consulting income or a patent. "Specificity" states whether the declared interest is a subject matter of the meeting or work to be undertaken. An interest has "financial significance" if the honoraria, consultancy fee or other received funding, including those received by expert's organization, from any single vaccine manufacturer or other vaccine-related company exceeds 5,000 USD in a calendar year. Likewise, a shareholding in any one vaccine manufacturer or other vaccine-related company in excess of 1,000 USD would also constitute a “significant shareholding”.

Last updated: 19 March 2018