Types of seasonal influenza vaccine
Injected trivalent inactivated influenza vaccines are most commonly used throughout the world. Influenza antigen preparation varies between manufacturers. The inactivated influenza vaccines available in the EU/EEA may contain either split virion influenza virus products or subunit influenza products. Adjuvanted inactivated subunit influenza vaccines for older people are available in some EU/EEA Member States.
Injected quadrivalent inactivated influenza vaccines, available from the 2014/2015 season in some EU/EEA countries, are expected to replace the trivalent vaccines over time. Although available in the private market in some European countries, vaccine authorisation, vaccine availability, observed vaccine effectiveness and the cost may influence the speed of this replacement.
In 2011, a live attenuated influenza vaccine (LAIV) for intranasal use was approved in the EU/EEA for children and adolescents (2-17 years of age). All live attenuated influenza vaccines currently available are quadrivalent combination vaccines containing two influenza A strains (H1N1 and H3N2 subtypes) and two influenza B strains (Victoria and Yamagata lineages) as per WHO recommendations.
The universal paediatric programmes organised in Finland and the United Kingdom offer quadrivalent LAIV to either young children 2-3 or 2-11 years of age, respectively.
Since seasonal influenza vaccines are usually recommended for several vulnerable populations who are poorer immune responders due to age or disease, several attempts to improve the vaccines have been explored over the last 10-15 years such as: increasing the antigen dose administered, intradermal administration to activate other arms of the immune system, and adding immunostimulating compounds such as adjuvants (See reference 1-4).
Products utilising these new techniques are now authorised and available in some EU/EEA countries. See table below. For human influenza vaccines, MF59 (squalene) and AS03 (squalene and α-tocopherol) have been approved as adjuvants by regulatory agencies in the EU, Canada and the United States. Data from several observational studies indicating improved performance and reductions in hospitalisations in older adults against influenza disease and hospitalisations have been included in the label for the adjuvanted trivalent influenza vaccine.
Most influenza vaccines, both inactivated and live attenuated, are based on production of influenza viruses/antigens in fertilised hens' eggs. These vaccines can therefore not be given to egg-allergic individuals developing severe symptoms upon exposure to egg proteins. Hence, a few manufacturers have developed cell-based influenza vaccines which can be given to severely egg-allergic individuals. Use of cell-based products may have an improved match to circulating influenza strains as they avoid egg-adaption issues.
Overview of available seasonal influenza vaccines in the EU/EEA (2019/20 season)
| Name of product | Manufacturer | Vaccine type | Adjuvant | Administration route | Produced in | Age recommended |
|---|---|---|---|---|---|---|
| 3Fluart | Fluart Innovative Vaccines Kft | Inactivated | Aluminium phosphate gel | Intramuscular | Egg | From 3 years |
| Afluria | Pfizer/Seqirus | Inactivated | None | Intramuscular | Egg | From 5 years |
| Agrippal | Seqirus | Inactivated/ subunit | None | Intramuscular | Egg | From 6 months |
| Fluad | Seqirus | Inactivated/ subunit | Squalene (MF59) | intramuscular | Egg | From 65 years |
| Fluarix | GlaxoSmithKline | Inactivated/ split | None | intramuscular/ subcutaneous | Egg | From 6 months |
| Fluarix Tetra | GlaxoSmithKline | Inactivated/ split | None | intramuscular | Egg | From 6 months |
| Flucelvax Tetra | Seqirus | Inactivated | None | intramuscular | Cell | From 9 years |
| Fluenz Tetra | AstraZeneca | Live attenuated | None | intranasal | Egg | From 24 months to 17 years |
| Imuvac | Abbot Biologicals/Mylan Products Ltd. (Marketing Authorisation Holder) | Inactivated | None | intramuscular | Egg | From 6 months |
| Influvac Xanaflu | Mylan Products Ltd. | Inactivated | None | intramuscular | Egg | From 6 months |
| Influvac Tetra | Mylan Products Ltd. | Inactivated | None | Intramuscular/ subcutaneous | Egg | From 3 years |
| Trivalent Influenza Vaccine High Dose | Sanofi Pasteur | split virion, inactivated | None | intramuscular | Egg | From 65 years |
| Vaxigrip Istivac Mutagrip | Sanofi Pasteur | Inactivated | None | Intramuscular/ subcutaneous | Egg | From 6 months |
| Vaxigrip Tetra | Sanofi Pasteur | Inactivated | None | Intramuscular/ subcutaneous | Egg | From 6 months |
| Xanaflu Tetra Fluvaccinol Subunit Tetra Batrevac Tetra Influenza vaccine Tetra MYL | Abbot Biologicals/Mylan Products Ltd. (Marketing Authorisation Holder) | Inactivated | None | Intramuscular/ deeply subcutaneous | Egg | From 3 years |
* The same product may be sold under different names ** Split virion by Triton X-100 and formaldehyde inactivated *** Beta-propriolactone-inactivated and taurodeoxycholate- split virion vaccine
Source of information: EMA and national regulatory authority websites
References
- Wilkinson K, Wei Y, Szwajcer A, Rabbani R, Zarychanski R, Abou-Setta AM, Mahmud SM. Efficacy and safety of high-dose influenza vaccine in elderly adults: A systematic review and meta-analysis. Vaccine. 2017 May 15;35(21):2775-2780. doi: 10.1016/j.vaccine.2017.03.092. Epub 2017 Apr 18.
- Marra F, Young F, Richardson K, Marra CA. A meta-analysis of intradermal versus intramuscular influenza vaccines: immunogenicity and adverse events. Influenza Other Respir Viruses. 2013 Jul;7(4):584-603. doi: 10.1111/irv.12000. Epub 2012 Sep 13.
- Domnich A, Arata L, Amicizia D, Puig-Barberà J, Gasparini R, Panatto D. Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis. Vaccine. 2017 Jan 23;35(4):513-520. doi: 10.1016/j.vaccine.2016.12.011.
- Chada KE, Forshee R, Golding H, Anderson S, Yang H. A systematic review and meta-analysis of cross-reactivity of antibodies induced by oil-in-water emulsion adjuvanted influenza H5N1 virus monovalent vaccines. Vaccine. 2017 May 31;35(24):3162-3170. doi: 10.1016/j.vaccine.2017.04.029. Epub 2017 May 5.
- Van Buynder PG, Konrad S, Van Buynder JL, Brodkin E, Krajden M, Ramler G, Bigham M. The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine. 2013 Dec 9;31(51):6122-8. doi: 10.1016/j.vaccine.2013.07.059. Epub 2013 Aug 6.
Availability of influenza vaccines by country in EU/EEA in the 2019/20 season
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