Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine

The annual trivalent influenza vaccine (TIV) includes viruses representing three influenza strains - one A/H1N1, one A/H3N2, and one B, although two antigenically distinct lineages of influenza B (Victoria and Yamagata) co-circulate annually in the United States. Predicting which lineage of influenza B will predominate during a season is challenging, and cross-protection by immunization against the other lineage is expected to be low. One proposed alternative is to produce a quadrivalent influenza vaccine (QIV) including an influenza B virus from each of the two circulating lineages. We estimated the additional public health benefit of QIV compared with TIV by calculating the expected impact on influenza-related health outcomes (illness, hospitalization, and death) over ten influenza seasons (1999/2000-2008/2009). We included data on the annual incidence of influenza-associated outcomes, virologic circulation, vaccine coverage, and vaccine effectiveness. We also considered annual vaccine production capacity, since available resources would have produced four vaccine viruses instead of three, potentially resulting in fewer doses of QIV. Use of QIV could have reduced annual cases (range: 2200-970,000), hospitalizations (range: 14-8200), and deaths (range: 1-485) in the US. During earlier seasons, adjusting production capacity for a fourth virus in QIV could have resulted in reduced overall influenza vaccine availability and net increases in influenza-associated outcomes. However, in recent seasons, the expected supply of QIV is likely to exceed the doses of vaccine actually administered. The potential net impact of QIV on influenza-associated outcomes is expected to vary between seasons, depending on annual variability in the incidence of influenza caused by the two influenza B lineages, vaccine coverage, and effectiveness. The additional protection provided by including a second lineage of influenza B could result in a modest reduction in influenza-associated outcomes.