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 vaccine for older people is available in some EU/EEA Member States and is since 2015 authorised for younger children in Canada but not yet in Europe (see table below).

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 organized 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. It is currently not clear if any of them perform better than the unadjuvanted vaccines although the first studies indicate better protection in the oldest age group (See reference 3, 5).

Most influenza vaccines, both inactivated and live attenuated, are based on production of influenza viruses/antigens in fertilized 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 As of autumn 2017 a cell-based product is under evaluation by the European Medicines Agency for central authorisation. The vaccine produced in Hungary is a cell-based vaccine, but this vaccine is only authorised for use in Hungary.

In total, seven influenza vaccine manufacturers produce and deliver seasonal influenza vaccines to EU/EEA countries. The majority of these influenza vaccines were authorised before the creation of the European Medicines Agency in 1995 and have therefore predominantly been approved by national regulatory agencies rather than centrally approved in the EU/EEA. As a result, some influenza vaccines are named differently in different countries, despite being the exact same product. The only exception is the recently introduced intranasal live attenuated influenza vaccine which was centrally authorised by the European Medicines Agency and uses one name in the EU/EEA (Fluenz tetra), but another in the US (Flumist quadrivalent).

    Overview of available seasonal influenza vaccines in the EU/EEA (2017/18 season)

    Manufacturer

    Name of product*

    Available for use in the following countries

    Vaccine type

    Adjuvant

    Administration route

    Produced in

    Age recommended

    Abbot Biologicals

    Trivalent:

    Influvac

    All EU/EEA countries

    Inactivated

    None

    intramuscular

    Egg

    From 6 months

    Imuvac

    UK

    AstraZeneca

    Quadrivalent:

    Fluenz tetra  

    Austria, Finland, Germany, Norway, Sweden, UK

    Live attenuated

    None

    intranasal

    Egg

    From 24 months to 17 years

    GlaxoSmithKline

    Trivalent: Fluarix** Alpharix Influsplit  

    Trivalent:

    All EU/EEA countries

     

    Inactivated/ split

    None

    Trivalent intramuscular/ subcutaneous

    Egg

    Trivalent: From 6 months

    Quadrivalent: From 3 years

    Quadrivalent: Fluarix Tetra Alpharix Tetra Influsplit Tetra

    Quadrivalent:

    Belgium, France, Germany, Italy, Spain, Switzerland, UK

    Quadrivalent intramuscular

    Seqirus

    Trivalent:

    Agrippal Fluvirin

    Trivalent:

    All EU/EEA countries

    Inactivated/ subunit

    None

    intramuscular

    Egg

    From 6 months

    Adjuvanted trivalent: Fluad

    Adjuvanted trivalent:

    Germany, Italy, Spain, Sweden, UK

    Squalene (MF59

    From 65 years

    Omninvest

    Trivalent:

    Fluval AB

     

    Hungary

    Inactivated

    Aluminium phosphate gel

    intramuscular

    Cell

    From 6 months

    Pfizer/CSL Australia

    Trivalent:

    Afluria*** Enzira

     

    Inactivated  

    None  

    intramuscular  

    Egg  

    From 5 years, however increased fever reported in children 6 months to 5 years

    Sanofi Pasteur

    Trivalent:

    Vaxigrip**

     

     

     

    Trivalent:

    Available in all EU/EEA countries

    Inactivated  

    None  

    Intramuscular/ subcutaneous  

    Egg  

    From 6 months  

    Trivalent:

    Istivac

    Portugal, Spain

    Intramuscular/ subcutaneous  

    From 6 months

    Trivalent:

    Mutagrip

    Italy, Spain

    Intramuscular/ subcutaneous  

    From 6 months

    Trivalent:

    Intanza

     

    Austria, UK

    Intradermal

    From 18 years

    Quadrivalent:

    Vaxigrip Tetra

    Quadrivalent:

    Austria, Belgium, Bulgaria, Croatia, Czech republic, Estonia, Finland, Germany, Greece, Hungary, Italy, Ireland, Latvia, Lithuania, Malta, Poland, Romania, Slovenia, Sweden, UK

    Intramuscular/ subcutaneous  

    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

    As noted above three vaccine manufacturers currently offer tetravalent influenza vaccines on the EU/EEA market: AstraZeneca, GSK and Sanofi Pasteur. These vaccines are as of 2017 only authorised in a limited number of EU/EEA countries. In most countries where quadrivalent vaccines are available there are still also trivalent influenza vaccines being used dependent on procurement agreements with different health care providers.

    To request an update of this table, please write to ECDC.Influenza@ecdc.europa.eu

    References

    1. 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.
    2. 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.
    3. 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.
    4. 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.
    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.

    All updates on influenza vaccination

    News

    WHO recommendations for influenza virus vaccine composition for the 2018-2019 Northern hemisphere season

    news, ECDC comment -

    News

    Low uptake of seasonal influenza vaccination in Europe may jeopardise capacity to protect people in next pandemic

    press release -

    Event

    E-learning course on how to increase influenza vaccination uptake

    News

    WHO recommendations for influenza virus vaccine composition for the 2018 southern hemisphere influenza season

    ECDC comment -

    Event

    Flu awareness week 2017

    16 Oct 2017 - 20 Oct 2017

    More about immunisation

    Immunisation and vaccines

    Vaccines represent one of the most effective and cost-saving public health intervention.

    Vaccine-preventable diseases

    Find out more about the diseases that vaccines prevent: latest updates, current and past disease threats and outbreaks, surveillance and disease data, preventive measures and basic disease facts.