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Rationale for a Quadrivalent Influenza Vaccine (QIV)

For more than a decade, almost all seasonal influenza disease in humans has been caused by strains of:

  • two influenza A subtypes: H1N1 and H3N2 [1][3]
  • two influenza B lineages: Yamagata and Victoria [1][3]

The genetic makeup of the circulating viruses changes every year which means that the flu vaccines have to be modified every year to provide the required protection. Each of the two B lineages, Victoria and Yamagata, are genetically distinct and produce a different immune response in the body.[3]

Type A and B influenza affect all age groups and are similar in clinical presentation and severity.[4]-[8]

Globally, 30% of seasonal influenza is caused by influenza B.[14]

Timeline of influenza-related events

Victoria-like strains were first detected around 1985. From 1987 to 1989, the Victoria lineage dominated global circulation, followed by Yamagata dominance in the 1990s and subsequent re-emergence of the Victoria lineage in 2001/2002. From 2001/2002 to the present, both lineages have co-circulated globally each season at varying levels.[3]

Figure 1: Adapted from McCullers JA et al.[9]

History of influenza

The rationale for a quadrivalent vaccine

It is difficult to predict which of the two B influenza lineages will be dominant in a given year for the following reasons:

  • Limited cross-protection between the two B lineages, so the effectiveness of each season’s TIV against influenza B depends on the correct prediction of the circulating B lineage. [2] [10]
  • Trivalent influenza vaccines (TIV) contain one strain from only one B lineage each year based on a WHO prediction of which will be most dominant [12]
  • Globally, Influenza B is responsible for approximately 30% of cases. B lineage circulation is unpredictable and co-circulation occurs most years. [14]
  • In 9 out of 10 years in the UK both B lineages were in circulation [11] (see graph below)
  • In 5 out of 10 years in the UK, TIVs did NOT contain the predominately circulating B lineage. [11]

So while Trivalent Influenza Vaccines (TIV’s) have helped protect millions, there remains a major gap in flu protection and the development of innovative vaccines is critical to help protect populations.

The development of Fluarix Tetra

Since 2012, the WHO has recommended not only the three strains to be included in TIV’s, but also a fourth from the alternative B lineage to be included in QIV’s.[12]

Fluarix Tetra is the UK’s first injectable Quadrivalent Influenza Vaccine (QIV), offering broad protection against two B strains as well as two A strains: [15]

- Enables you to protect against one strain from each B lineage as well as the two predicted A subtypes [15]

- Gives a broader level of protection against influenza than TIVs [15]

The use of QIVs containing a strain from each B lineage is expected to improve the matching of influenza vaccines in the future. JCVI has advised that, all other things being equal, quadrivalent inactivated vaccines are preferable to trivalent inactivated vaccines.[13]


  1. WHO. Fact sheet no 211 – influenza (seasonal). [Last accessed August 2016]
  2. Belshe RB. The need for quadrivalent vaccine against seasonal influenza. Vaccine. 2010; 28 (suppl 4): D45–D53.
  3. Ambrose CS, Levin MJ. The rationale for quadrivalent influenza vaccines. Hum Vaccin Immunother. 2012; 8: 81–88.
  4. Irving SA, et al. Comparison of clinical features and outcomes of medically attended influenza A and influenza B in a defined population over four seasons: 2004–2005 through 2007–2008. Influenza Other Respir Viruses. 2012; 6: 37–43.
  5. Paddock CD, et al. Myocardial injury and bacterial pneumonia contribute to the pathogenesis of fatal influenza B virus infection. J Infect Dis. 2012; 205: 895–905.
  6. Peltola V, et al. Influenza A and B virus infections in children. Clin Infect Dis. 2003; 36: 299–305.
  7. Daley AJ, et al. Comparison of influenza A and influenza B virus infection in hospitalized children. J Paediatr Child Health. 2000; 36: 332–335.
  8. Hite LK, et al. Medically attended pediatric influenza during the resurgence of the Victoria lineage of influenza B virus. Int J Infect Dis. 2007; 11: 40–47.
  9. McCullers JA & Huberb VC (2012) Correlates of vaccine protection from influenza and its complications. Human Vaccines & Immunotherapeutics. 8 (1); 34-33
  10. Van Bellinghen LA, et al. (2014) The potential cost-effectiveness of quadrivalent versus trivalent influenza vaccine in elderly people and clinical risk groups in the UK: a lifetime multi-cohort model. PLoS One. 9(6): e98437
  11. HPA/PHE data. 2005/06-2015/16 published annual influenza reports. [Last accessed: August 2016].
  12. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2015-2016 northern hemisphere influenza season. February 2016. [Last accessed August 2016] 
  13.  Green Book, Chapter 19: Influenza. Last updated: 28 August 2015.
  14.  WHO Influenza viriological updates, last updated: 25th July 2016. [Last accessed: 3rd August 2016]
  15.  Fluarix™ Tetra SPC. [Last accessed August 2016]

Adverse events should be reported. Reporting forms and information can be found at
Adverse events should also be reported to GlaxoSmithKline UK on 0800 221 441.

Fluarix Tetra is a registered trademark of the GlaxoSmithKline Group of Companies