Abstract

BackgroundInfluenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 20 million new episodes of ALRI in children annually, 97% of these occurring in developing countries. It is also estimated to result in 28000 to 112000 deaths annually in young children. Apart from hospitalisations and deaths, influenza has significant economic consequences. The current egg-based inactivated influenza vaccines have several limitations: annual vaccination, high production costs, and cannot respond adequately to meet the demand during pandemics.MethodsWe used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging cross-protective vaccines against influenza relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.ResultsThe experts expressed very high level of optimism for deliverability, impact on equity, and acceptability to health workers and end users. However, they expressed concerns over the criteria of answerability, low development cost, low product cost, low implementation cost, affordability and, to a lesser extent sustainability. In addition they felt that the vaccine would have higher efficacy and impact on disease burden reduction on overall influenza-associated disease rather than specifically influenza-associated pneumonia.ConclusionAlthough the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production.

Highlights

  • Influenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children

  • Answerabilty - Is the science behind the research viable? Adjuvanted egg-based inactivated vaccines (EBIV) Adjuvanted vaccines (Figure 3) have been shown to be antigen sparing and more immunogenic compared to non-adjuvanted vaccines, and may allow increased production capacity to meet global demand [30,31,32]

  • - Included research into influenza vaccine, or other vaccine that may bear resemblance to future influenza vaccination programs - Vaccine research was targeted at children under 5 years - Gave an indication of answerability, efficacy, effectiveness, deliverability, disease burden reduction or impact on equity of a vaccine

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Summary

Introduction

Influenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children. The current egg-based inactivated influenza vaccines have several limitations: annual vaccination, high production costs, and cannot respond adequately to meet the demand during pandemics. Acute lower respiratory infections (ALRI) are a leading cause of morbidity and mortality in young children [1,2]. The ability of the current egg-based inactivated vaccines to successfully provide long-term immunity is limited by antigenic drift (minor mutations causing small changes in the haemagglutinin gene); or the rarer antigenic shift (genetic re-assortment between animal and human influenza viruses; or a direct jump from animal species to humans of a virus that has acquired the ability to spread from human-to-human). The paper is presented as part of a series of papers addressing emerging vaccines and other interventions against pneumonia [11,12,13,14,15,16]

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