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Adjuvanted influenza vaccines.

ABSTRACT: In spite of current influenza vaccines being immunogenic, evolution of the influenza virus can reduce efficacy and so influenza remains a major threat to public health. One approach to improve influenza vaccines is to include adjuvants; substances that boost the immune response. Adjuvants are particularly beneficial for influenza vaccines administered during a pandemic when a rapid response is required or for use in patients with impaired immune responses, such as infants and the elderly. This review outlines the current use of adjuvants in human influenza vaccines, including what they are, why they are used and what is known of their mechanism of action. To date, six adjuvants have been used in licensed human vaccines: Alum, MF59, AS03, AF03, virosomes and heat labile enterotoxin (LT). In general these adjuvants are safe and well tolerated, but there have been some rare adverse events when adjuvanted vaccines are used at a population level that may discourage the inclusion of adjuvants in influenza vaccines, for example the association of LT with Bell's Palsy. Improved understanding about the mechanisms of the immune response to vaccination and infection has led to advances in adjuvant technology and we describe the experimental adjuvants that have been tested in clinical trials for influenza but have not yet progressed to licensure. Adjuvants alone are not sufficient to improve influenza vaccine efficacy because they do not address the underlying problem of mismatches between circulating virus and the vaccine. However, they may contribute to improved efficacy of next-generation influenza vaccines and will most likely play a role in the development of effective universal influenza vaccines, though what that role will be remains to be seen.

SUBMITTER: Tregoning JS

PROVIDER: S-EPMC5861793 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Adjuvanted influenza vaccines.

Tregoning John S JS Russell Ryan F RF Kinnear Ekaterina E

Human vaccines & immunotherapeutics 20180125 3

In spite of current influenza vaccines being immunogenic, evolution of the influenza virus can reduce efficacy and so influenza remains a major threat to public health. One approach to improve influenza vaccines is to include adjuvants; substances that boost the immune response. Adjuvants are particularly beneficial for influenza vaccines administered during a pandemic when a rapid response is required or for use in patients with impaired immune responses, such as infants and the elderly. This r ...[more]

PMID: 29232151

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Project description: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.

Dataset Information

Adjuvanted influenza vaccines.

Publications

Adjuvanted influenza vaccines.

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