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Author Notes:

Correspondence: Amanda L. Wilkins tolson.amanda@gmail.com

AW, DK, GN, and EC wrote the initial drafts for the manuscript which was then revised and contributed to by BP, C-AS, and AP.

C-AS has received numerous educational or research grants, including from vaccine manufacturers, although none related to this work.

AP has previously conducted clinical studies on behalf of Oxford University that were sponsored by vaccine manufacturers with grants from Okairos and Pfizer closing since January 2015.

His department received unrestricted educational grants from Novartis/GSK/Astra Zeneca in 2015, Pfizer/GSK/Astra Zeneca in July 2016, and Gilead/MSD/GSK/Astra Zeneca in June 2017 to support a 3-day course on Infection and Immunity in Children.

He is Chair of UK Dept. Health’s (DH) Joint Committee on Vaccination and Immunization (JCVI) and chair of the scientific advisory group on vaccines for the European Medicines Agency and is a member of the WHO’s SAGE.

The views expressed in this manuscript do not necessarily represent the views of DH, JCVI or WHO.

All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

This study was supported in part by European Commission FP7 Grant “Advanced Immunization Technologies (ADITEC)” and the National Institute for Health Research Oxford Biomedical Research Centre.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • adjuvant
  • influenza vaccine
  • MF59
  • AS03
  • children
  • MEMORY B-CELLS
  • A(H1N1) PANDEMIC INFLUENZA
  • FOLLICULAR HELPER-CELLS
  • YELLOW-FEVER VACCINE
  • A H1N1 VACCINES
  • SEASONAL INFLUENZA
  • YOUNG-CHILDREN
  • ANTIBODY-RESPONSES
  • VIRUS-INFECTION
  • IMMUNE-RESPONSES

AS03-and MF59-Adjuvanted influenza vaccines in Children

Tools:

Journal Title:

Frontiers in Immunology

Volume:

Volume 8, Number DEC

Publisher:

, Pages 1760-1760

Type of Work:

Article | Final Publisher PDF

Abstract:

Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility of novel approaches in understanding new adjuvants and their importance for developing improved influenza vaccines for children.

Copyright information:

© 2017 Wilkins, Kazmin, Napolitani, Clutterbuck, Pulendran, Siegrist and Pollard.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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