Terms of Reference

• Review and summarize the measured and modelled evidence on pneumococcal conjugate vaccines (PCV) immunogenicity and impact (direct and indirect) on carriage, disease, and mortality with respect to the following questions/issues:
• Effectiveness and/or impact of different schedules and strategies for PCV use in industrialized and developing countries including effectiveness of incomplete schedules;
• Preference for a 2p+1 or a 3p+0 schedule;
• Descriptions of PCV performance and programmatic characteristics relevant to product choices, including interchangeability of PCV products;
• Effect of catch-up vaccination of infants and/or older age groups at the time of PCV introduction;
• Maximizing herd protection;
• Optimizing duration of protection
• Propose recommendations to SAGE on optimal PCV use related to the above listed questions and issues. These recommendations will be used to update the 2012 WHO position paper on PCV.
• Identify and prioritize knowledge gaps and critical questions to prepare a concrete scope of work with a proposed timeline for future PCV working group activities. The following questions/issues will likely be included:
• Serotype replacement in the era of expanded valency conjugate vaccines;
• Options for optimal PCV use in the future, including in settings of near-elimination levels of vaccine serotype disease;
• PCV use in adults, including the elderly;
• Incremental benefit of the polysaccharide vaccine in adults in era of PCV use.
• Provide SAGE with summaries and analyses needed to support its discussion and recommendation process.

Composition

SAGE Members

• Peter McIntyre: Dunedin School of Medicine, University of Otago, New Zealand
• Andrew J. Pollard: University of Oxford, United Kingdom (Chair of the Working Group)

Experts

• Narendra Arora: The INCLEN Trust International, India
• Stefan Flasche: London School of Hygiene & Tropical Medicine, United Kingdom
• Kyung-Hyo Kim: Ewha Womans University School of Medicine, Republic of Korea
• David Goldblatt: University College London, United Kingdom
• Elisabeth Lieke Sanders1: National Institute for Public Health and the Environment, The Netherlands
• Dafrossa Lyimo: Ministry of Health, Tanzania
• Elizabeth Miller: Public Health England, United Kingdom
• Edward Kim Mulholland: Murdoch Childrens Research Institute, Australia
• Kate O'Brien: Johns Hopkins University, USA
• Tamara Pilishvili: Centers for Disease Control and Prevention, United States of America
• Betuel Sigauque: Manhiça Health Research Centre, Mozambique
• Cristiana Toscano: Federal University of Goiás, Brazil

WHO Secretariat

• Shalini Desai (Focal Point)

Declaration of interests

All members completed a declaration of interests. Seven members reported relevant interests. All interests were assessed not to constitute a conflict of interest. It was concluded that all members could take part in full in all of the discussions. The reported relevant interests are summarized below:

SAGE members

Kate O’Brien

• She serves as technical expert consultant for Merck, ClearPath, Affinivax and PATH on pneumococcal vaccination. This interest was assessed as non-personal, specific and financially insignificant*.
• She 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 personal, non-specific and financially significant*.
• She 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, the Bill and Melinda Gates Foundation regarding pneumococcal, rotavirus vaccines, technical country support and decision making on pneumococcal/rotavirus vaccine, vaccine demand support, and/or pneumonia etiology. This interest was assessed as non-personal, specific and financially significant*.
• Her institution received research grants from the National Institutes of Health (NIH) regarding PCV 13. This interest was assessed as non-personal, specific and financially significant*.
• Her institution currently receives research grants from Merck on the value of adult vaccine preventable diseases. This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution received research grants from Merck on the adult vaccine initiative until June 2016. This interest was assessed as non-personal, non-specific and financially significant*.

Andrew J. Pollard

• His institution1 received research support until 2014 from GSK on Pneumococcal vaccine. This interest was assessed as non-personal, specific and financially significant*.
• His institution received research support expected to end in 2016 from Okairos on RSV vaccine. This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support until 2015 from Pfizer on Meningococcal B vaccine, meningitis epidemiology and pneumococcal epidemiology. This interest was assessed as non-personal, specific and financially significant*.
• His institution received research support until 2014 from Novartis on Meningococcal B vaccine. This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support on a grant for a study an Ebola vaccine developed by Janssen (2015-current) funded by a European Commission IMI grant (EBOVAC). This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support on a grant for a study on the cause of fever with Bexsero funded by a European Commission grant (EUCLIDS; funding 2011-2016). The vaccine for the study is provided by Novartis /GSK. This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support on a grant for a study on the efficacy of a typhoid vaccine (Tybar-CV) produced by Bharat Biotech, India (2013-2016) funded by the Bill and Melinda Gates Foundation. No funding was received from Bharat Biotech, the grant was funded by the Bill and Melinda Gates Foundation. This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support on a grant for a study on the genes expressed in children when they receive an adjuvanted influenza vaccine (FluAd, Novartis) funded by a European Commission grant (ADITEC, 2011-2016). This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support on a grant for a study on the treatment of encephalitis in children with intravenous immunoglobulin (supply and distribution funding agreement with CSL Behring) funded by the National Institute for Health Research (2015-2020). This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support on a grant for a study on the infant pneumococcal vaccine schedule in Nepal (2013-2017), funded by Gavi, the Vaccine Alliance. This interest was assessed as non-personal, specific and financially significant*.
• His institution received unrestricted educational grants from Novartis/GSK/Astra Zeneca/Sanofi Pasteur MSD in 2014; Novartis/GSK/Astra Zeneca in 2015 and Pfizer/GSK/Astra Zeneca in 2016 for a course on infection and immunity in children. This interest was assessed as non-personal, non-specific and financially significant*.
• His institution received research support until 2014 from SPMSD on a hexavalent infant vaccine. This interest was assessed as non-personal, non-specific and financially significant*.

Experts

Kyung-Hyo Kim

• Her institution received a research grant from GSK, regarding meningococcal carriage in healthy adolescents (2015). This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution currently receives a research grant from the Ministry of Food and Drug Safety (MFDS) in Republic of Korea regarding vaccine evaluation of Hib, pneumococci, meningococci, hepatitis A, measles, mumps, and rubella (2009-current). This interest was assessed as non-personal, specific and financially significant*.
• Her institution received a research grant from the Korean Centers for Diseases Control & Prevention regarding pneumococcal polysaccharide vaccine evaluation for the national immunization program (2013). This interest was assessed as non-personal, specific and financially significant*.
• Her institution received a research grant from the National Research Foundation in Korea for a null capsule clade pneumococci study (2013-2016). This interest was assessed as non-personal, specific and financially significant*.
• Her laboratory, Ewha Center for Vaccine Evaluation and Study, currently provides support for opsonophagocytosis assay (OPA) for assessing the immune response following vaccination with pneumococcal conjugate vaccines to LG Life Science. As a reference laboratory, they process anonymized samples and return the results to LG Life Science. This interest was assessed as non-personal, specific and financially significant*.
• Her laboratory currently provides support for anti-PRP antibody assays (EIA and serum bactericidal assay) for assessing the immune response following vaccination with Hib or Hib-containing combination vaccines to LG Life Science. As a reference laboratory, they process anonymized samples and return the results to LG Life Science. This interest was assessed as non-personal, non-specific and financially significant*
• Her laboratory currently provides research support for anti-PRP antibody assays (EIA) for assessing the immune response following vaccination with Hib vaccine. As a reference laboratory, they process anonymized samples and return the results to LG Life Science. This interest was assessed as non-personal, non-specific and financially significant*
• Her laboratory was provided financial support for OPA for assessing the immune response following vaccination with pneumococcal conjugate vaccines to SK Chemical. As a reference laboratory, they process anonymized samples and return the results to SK Chemical (2013-2014). This interest was assessed as non-personal, specific and financially significant*.
• Her institution currently receives research support from Sanofi Pasteur for the clinical trial of meningococcal conjugate vaccine in Korea children. This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution currently receives research support from SK Chemical, Korea for the clinical trial of PCV13 in Korean children. This interest was assessed as non-personal, specific and financially significant*.
• Her institution currently receives research support from Boryung Korea for the clinical trial of Japanese encephalitis vaccine in Korean children. This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution currently receives research support from Norvatis for the clinical trial of meningococcal conjugate vaccine in Korean adolescents. This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution currently receives research support from Merck for the clinical trial of HPV vaccine in Korean children and adolescents. This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution received research support from Norvatis for the clinical trial of meningococcal serogroup B vaccine in Korean adolescents (2013-2014). This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution received research support from Merck for the clinical trial of meningococcal conjugate vaccine in Korean children and adolescents (2013). This interest was assessed as non-personal, specific and financially significant*.

David Goldblatt

• He received financial compensation from Merck for Advisory Board Activity focused on adult vaccination, global vaccines and an Advisory Board on the development of a novel PCV vaccine (2013-2014). This interest was assessed as personal, specific and financially significant*.
• He received financial compensation from GSK for Advisory Board Activity focused on protein vaccines (2013-2015). This interest was assessed as personal, non-specific and financially significant*.
• He received financial compensation from Sanofi Pasteur for Advisory Board Activity focused on protein vaccines (2013-2015). This interest was assessed as personal, non-specific and financially significant*.
• His laboratory, which is a WHO reference laboratory for serological assays for assessing the immune response following vaccination with pneumococcal conjugate vaccines, provides support for assays to Merck. As a reference laboratory, they process anonymized samples and return the results to Merck. This interest was assessed as non-personal, specific and financially insignificant*.
• His laboratory, which is a WHO reference laboratory for serological assays for assessing the immune response following vaccination with pneumococcal conjugate vaccines, provides support for assays to Sanofi Pasteur. As a reference laboratory, they process anonymized samples and return the results to GSK. This interest was assessed as non-personal, specific and financially insignificant*.
• His laboratory, which is a WHO reference laboratory for serological assays for assessing the immune response following vaccination with pneumococcal conjugate vaccines, provides support for assays to Sanofi Pasteur. As a reference laboratory, they process anonymized samples and return the results to Sanofi Pasteur. This interest was assessed as non-personal, specific and financially insignificant*.

Elisabeth Lieke Sanders

• Her institution received a grant from GSK to study a 4-valent meningococcal conjugate vaccine in adolescents and the immunology of booster vaccination (2013-2016). This interest was assessed as non-personal, non-specific and financially significant*.
• Her institution received a grant from GSK to study the epidemiology of invasive pneumococcal infections in the Netherlands (2013-2015). This interest was assessed as non-personal, specific and financially significant*.
• Her institution received a grant from GSK to investigate the population structure of pneumococcal invasive disease isolates in the Netherlands (2013-2015). This interest was assessed as non-personal, specific and financially significant*.
• Her institution received a grant from Pfizer to study pneumococcal carriage in healthy adults (2013-2016). This interest was assessed as non-personal, specific and financially significant*.
• Her institution received a grant from Pfizer for multi-serotype meningococcal carriage in children and adults (2013-2016). This interest was assessed as non-personal, non-specific and financially significant*.

Edward Kim Mulholland

• He received financial compensation from Merck for Advisory Board Activity for a one-day meeting on adult immunization with 23-valent pneumococcal polysaccharide vaccine (2014). This interest was assessed as non-personal, specific and financially insignificant*.
• His institution1 currently receives a grant from GSK for PCV10 vaccine and OPA testing for a current Vietnam trial. This interest was assessed as non-personal, specific and financially significant*.
• He received financial compensation from GSK to speak at a company session at the World Society for Pediatric Infectious Diseases (WSPID) (2013). This interest was assessed as non-personal, non-specific and financially insignificant*.

Cristiana Toscano

• She received a grant from the WHO Pan American Health Organization/Sabin Vaccine Institute for technical support to a research project to assess PCV impact on the proportion of cases unvaccinated (PCU) in Latin America (2014). This interest was assessed as personal, specific and financially significant*.
• She received a grant from the Sabin Vaccine Institute for research support to conduct a systematic review on PCV impact in Latin America (2016). 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”. Funding going to the expert’s research unit needs to be declared.