WHO issues recommendation on the composition of influenza virus vaccines for the northern hemisphere 2015-2016

World Health Organization, Geneva, Switzerland – 26 February 2014

The World Health Organization (WHO) has agreed on the recommended composition of the trivalent influenza vaccine for the northern hemisphere 2015-2016 influenza season as:

• an A/California/7/2009 (H1N1)pdm09-like virus;
• an A/Switzerland/9715293/2013 (H3N2)-like virus;
• a B/Phuket/3073/2013-like virus (Yamagata lineage).

For quadrivalent vaccines containing two influenza B viruses the above three viruses and a B/Brisbane/60/2008-like virus (Victoria lineage) should be included.

The recommendation is the same as for southern hemisphere 2015 winter influenza season.

With this recommendation, two of the vaccine components, the A(H3N2) and B virus, will be changed in the trivalent vaccines in comparison to the composition of the northern hemisphere vaccine in 2014-2015. The reason for the change [PDF] is that increasing proportions of the recently circulating A(H3N2) and B Yamagata-lineage viruses have undergone antigenic drift since the last vaccine recommendation. All the (sub)types of influenza viruses have been circulating in the northern hemisphere with varied activities. Further antigenic and genetic characteristics of recent seasonal influenza viruses are described in the full report of the recommendation [PDF].

Influenza A(H1N1)pdm09 viruses

The A(H1N1)pdm09 viruses remain antigenically homogeneous and closely related to the earlier vaccine virus A/California/7/2009 and therefore there is no change in the recommendation for this component. The sequence analysis of the HA genes of A(H1N1)pdm09 viruses indicated that the viruses fell within two genetic groups, genetic clades 6B.

Influenza A(H3N2) viruses

Many of the A(H3N2) viruses circulating from September 2014 to January 2015 have shown antigenic drift from the earlier vaccine virus A/Texas/50/2012 (the northern hemisphere 2014-2015 vaccine component) and therefore a change in the recommendation is made to change the A(H3N2) vaccine component to a virus representing more closely the recently circulating viruses. The recent viruses are represented by an A/Switzerland/9715293/2013 (H3N2)-like virus in the new recommendation. The recently circulating viruses were not well recognised by ferret antisera raised against cell-propagated reference viruses such as A/Texas/50/2012 being inhibited in HI assays at a lower titer of antiserum. The HA genes of recent A(H3N2) viruses fell into two new main phylogenetic groups (3C.3a and 3C.2a) that were both antigenically distinguishable from previously circulating viruses but were antigenically related to each other. Antigenic characterization of A(H3N2) viruses, particularly 3C.2a viruses, has become technically difficult and require extensive investigations in multiple laboratories.

Influenza B viruses

The B/Yamagata/16/88 and the B/Victoria/2/87 lineage viruses have continued to co-circulate across the world with a predominance of the B/Yamagata lineage.

The majority of circulating viruses of the B/Yamagata/16/88 lineage fell genetically within two groups, clades 2 and 3. The recent B/Yamagata viruses that fell into the predominating clade, clade 3, were antigenically distinguishable from the previous vaccine virus of the B/Yamagata/16/88 lineage (B/Massachusetts/2012), and therefore a change to the composition of the vaccine for the B virus component was recommended. The recently circulating viruses are at the moment best represented by viruses that are B/Phuket/3073/2013-like.

The majority of viruses of the B/Victoria/2/87 lineage were antigenically closely related to the earlier vaccine virus B/Brisbane/60/2008. That virus has been recommended as a component of the quadrivalent vaccines in the northern hemisphere. There was no antigenic drift observed in the B/Victoria lineage viruses. The recommendation for the B/Victoria lineage vaccine component has not changed in comparison to the northern hemisphere 2014-2015 seasonal influenza vaccine recommendation.

ECDC comment

The given recommendation is well in line with the currently circulating viruses. However, A(H3N2) and B/Yamagata viruses continue to drift and it is difficult to predict with confidence as yet the vaccine match in season 2015-2016. For A(H3N2) viruses the question of how long it will take for the 3C.2a viruses to drift away from the current vaccine component A/Switzerland/9715293/2013-like virus remains. The technical difficulties in virus culture, characterisation and egg propagation of A(H3N2) viruses, make the selection of new vaccine components more difficult.

For the B/Yamagata clade 2 and 3 viruses, sufficient antigenic homology exists between the clades and therefore it is likely that the NH vaccine B/Yamagata component would protect against the circulating viruses of both genetic clades.

For the season 2014-2015, little or no vaccine effectiveness (VE) has been observed, especially against the dominant subtype A(H3N2) due to the mismatch in the vaccine component against the majority of the circulating viruses. For A(H1N1)pdm09 and B components the (sub)type level VE data is not yet available and may be difficult to obtain due to low levels of circulation.

WHO has put in place a process for improving the vaccine selection focussing on ensuring timely availability of representative influenza viruses for vaccine virus selection and on introduction of new technologies, materials and products relevant to vaccine virus selection.

Of note is also that a sharp increase of A(H5N1) human cases in Egypt and continued evolution of A(H5N1) viruses prompted inclusion of A/Egypt/N04915/2014-like virus as a candidate vaccine virus (CVV), on top of the existing A(H5N1) CVVs. The development of candidate vaccine viruses for pandemic preparedness and the current CVVs are listed in WHO documentation.