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 
- two influenza B lineages: Yamagata and Victoria 
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.
Globally, 30% of seasonal influenza is caused by influenza B.
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.
Figure 1: Adapted from McCullers JA et al.
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.  
- 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 
- Globally, Influenza B is responsible for approximately 30% of cases. B lineage circulation is unpredictable and co-circulation occurs most years. 
- In 9 out of 10 years in the UK both B lineages were in circulation  (see graph below)
- In 5 out of 10 years in the UK, TIVs did NOT contain the predominately circulating B lineage. 
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.
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: 
- Enables you to protect against one strain from each B lineage as well as the two predicted A subtypes 
- Gives a broader level of protection against influenza than TIVs 
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.
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Fluarix Tetra is a registered trademark of the GlaxoSmithKline Group of Companies