Doctoral thesis
OA Policy
English

Towards Single-Dose Pandemic Influenza Vaccines: Investigating Delayed Release and Adjuvanted Aproaches in the Context of Technology Transfer to Indonesia

ContributorsLemoine, Céline
Number of pages272
Imprimatur date2021-09-24
Defense date2021-09-17
Abstract

Influenza is a common virus that causes respiratory disease and is described by its characteristic enveloped negative-sense single-strand viral RNA (sRNA) and protruding surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Immune responses must adapt to structural changes in these surface proteins due to the accumulation of genetic point mutations in the sRNA. Of the different genera, Influenza A can infect the largest range of hosts including birds, swine, horses, dogs, marine mammals and humans. This can lead to genetic reassortment of two or more viral strains that have co-infected the same host resulting in a novel virus with pandemic potential. The threat of an emerging influenza virus of zoonotic origin is well recognized. The best tool to mitigate the detrimental effects of an influenza pandemic is vaccination. This can be as a pre-pandemic vaccine developed in advance of the emergence based on a virus strain with pandemic potential, however, these typically have limited efficacy. Alternatively, a pandemic vaccine, specific to the novel emerged strain, would need to be developed and will not be available at the onset of an outbreak. In order to accelerate such a manufacturing process and to enable sufficient vaccine coverage, also in consideration of the expected limited vaccine production capacities, research and development (R&D) on vaccine and adjuvant technologies are required. Adjuvant technologies can enhance the immune responses in elderly, achieve dose-sparing, or potentially enable effective single-dose vaccines. Adjuvanted vaccine development is concentrated in a small number of (western) countries, as the situation presents itself currently, and this forms a limiting factor to equitable access to vaccines as is the case for several low- and middle-income countries (LMICs). Increasing local capacities could increase product development opportunities, thereby, access to vaccines. Furthermore, establishing such capacities in countries with a (more) profound risk for an emerging influenza strain could be beneficial to enable a more rapid, local response, possibly preventing an endemic outbreak to become a pandemic. The fact that pandemic influenza vaccine development has to deal with a moving target is already a significant challenge on its own. The suboptimal immunogenicity of avian influenza vaccines in humans is another challenge that typically requires high vaccine doses and vaccination regimens consisting of two or more immunizations. Pandemic influenza vaccines that enable dose sparing and are effective as a single-dose vaccine currently do not exist – but would be a significant benefit in the context of an influenza pandemic. The principle aim of the research in this thesis was to develop single-dose pandemic influenza vaccines that are suitable for transfer to vaccine researchers and developers in LMICs.

Keywords
  • Influenza
  • Pandemic
  • Adjuvant
  • Delayed-Release
  • Microparticle
  • PLGA
Affiliation entities
Research groups
Citation (ISO format)
LEMOINE, Céline. Towards Single-Dose Pandemic Influenza Vaccines: Investigating Delayed Release and Adjuvanted Aproaches in the Context of Technology Transfer to Indonesia. Doctoral Thesis, 2021. doi: 10.13097/archive-ouverte/unige:156596
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Creation04/11/2021 16:46:00
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