Immunization, Vaccines and Biologicals

Call for nomination for experts to serve on the SAGE working group on influenza vaccines


A SAGE Working Group on influenza vaccines and immunization was established previously (2010-2014) to review data on the use of seasonal influenza vaccine in priority target groups with a focus on low- and middle-income countries and propose recommendations to SAGE. This led to the 2012 WHO position paper on influenza vaccine.

Over the last year, there have been a number of issues arising with influenza vaccines that require consideration by SAGE either now or in the near future when more data becomes available. These include:

  • Live attenuated influenza vaccines

Live attenuated influenza vaccines (LAIVs) have been used in the USA for nearly two decades, and have been introduced in numerous countries since, where they have demonstrated significant programmatic advantages. Most of the seasonal LAIVs use an attenuated influenza backbone based on the Ann Arbor strain. Other LAIVs use a backbone based on the Leningrad strain, though these are currently not widely available. Prior to the 2009 season, the Ann Arbor-derived vaccines demonstrated efficacy that was generally equal to or superior to the inactivated vaccines in the same age groups. Since 2010 low efficacy, particularly of the H1N1 strain, was observed in some studies though not in others. Specific countries’ recommendations to no longer use LAIV will likely impact on the supply of this type of vaccine. While these vaccines still offer programmatic and immunological advantages, further studies are urgently needed to understand why in some cases the effectiveness of LAIV is low. In 2017/18 additional studies will provide information on efficacy and effectiveness of the LAIV vaccines which may lead to a need for a review of the utility of these vaccines.

  • Adjuvanted seasonal vaccine for infants.

Canada approved the use of seasonal influenza vaccine containing the adjuvant MF59™ for use in infants in 2016, and the vaccine will be used in the upcoming season providing the first measure of effectiveness in this age group. Clinical studies had suggested that this vaccine has superior immunogenicity, efficacy and breadth of protection in young infants than the standard non-adjuvanted vaccine. As data become available from the 2017 season it will be necessary to evaluate whether there is a need to consider expanding recommendations for seasonal influenza vaccines to include adjuvanted vaccines.

  • Influenza vaccines for older adults

Older adults are one of the priority groups identified for influenza vaccines in the 2012 WHO position paper. However the efficacy of standard influenza vaccines in this group is often sub-optimal. Several vaccine formulations have been developed to address this, including high-dose vaccines containing 3-times as much antigen, adjuvanted vaccines and intradermal vaccines. As data on the efficacy and effectiveness of these vaccines will become available, proposing specific recommendations on these formulations may be required.

  • 3-valent vs 4-valent influenza vaccine

The additional benefit conferred by the 4-valent vs the 3-valent influenza vaccine needs to be assessed. Numerous manufacturers have begun switching their production from the trivalent to 4-valent formulation, which increases the cost of the vaccine. This may result in a reduced supply of trivalent vaccines and increase the cost of procuring vaccines. Several developing-countries and developing-country manufacturers are requesting advice on the necessity of transitioning to 4-valent vaccines and whether the added benefit is worth the cost.

  • The effect of repeat vaccinations.

There have been observations that annual influenza vaccination results in reduced titers to one or more of the strains, reduced effectiveness to one or more of the strains, and in some cases even suggestion of increased susceptibility to one or more of the strains. This phenomenon was first observed in the 1970s leading the authors to conclude that there was no long-term advantage to annual influenza vaccination. However subsequent studies and clinical trials found no consistent pattern of reduced vaccine effectiveness. Published research has found that prior influenza vaccination can provide residual protection against influenza in some years and can decrease vaccine effectiveness during other years,. These findings have not been consistently demonstrated from year to year, or among studies in different sites using similar methods in the same year.

On 19 July 2016 WHO convened a consultation with experts in influenza vaccine evaluation, epidemiology, immunology, and public health to better understand the existing data, to determine possible immunological mechanisms that could be involved, and to recommend research activities to better understand the reported findings. The experts advised that the current evidence is limited and contradictory and that further studies are needed.

Given that this effect can on occasion lead to reduced effectiveness, it is essential for WHO to consider the overall impact of this effect, and determine at what point any change to current policy should be envisaged. Data are still fragmentary, and there may be insufficient evidence at the moment for any change in policy.

In addition to these specific topics there is a continual emergence of evidence related to the use of influenza vaccines that needs to be considered for potential revision of existing or development of new recommendations.

Proposal for a staggered Working Group approach

Given that for most of the above topics there are only limited data available to date, it is proposed to proceed in a staggered manner: initially the Working Group is asked to review the available data and ongoing studies to determine research gaps and to assess at what time point there will be adequate data to permit a reconsideration of policy; followed by a second stage where the Working Group is asked to review whether a change in policy is required.

Terms of reference

The Working Group will be requested to review the scientific evidence and relevant programmatic considerations to assess whether there is sufficient evidence to inform a revision of the global policy on the use of influenza vaccines, and for subsequent updating of the WHO position paper on influenza vaccines.

Specifically the Working Group will be asked to review the following elements:

  • The evidence on the effect of prior immunization on the efficacy and effectiveness of seasonal influenza vaccines, and whether a change in policy would result in improved public health outcomes;
  • The evidence on the effectiveness of adjuvanted seasonal influenza vaccines in pediatric populations;
  • The evidence on the effectiveness of improved formulations for influenza vaccines for older adults and other risk groups;
  • The evidence on the effectiveness of live attenuated influenza vaccines.

Expertise needed in the WG

  • Influenza vaccine immunology and clinical evaluation methods.
  • Fundamental immunology with particular understanding of B- and T-cell effector functions.
  • Influenza virology with a particular understanding of viral competition in multivalent vaccines.
  • Epidemiology/public health expertise, with particular experience in low- and middle-income–countries and vaccine effectiveness studies.
  • Health economics.

Proposals for nominations should be sent by email to with a Curriculum Vitae, indication of relevant expertise, and a completed declaration of interest form. Only complete nominations received by Friday, 27 October 2017 will be considered.