The large variations in both the HA and NA sequences during the transitional period between Mos/10/99 and Fuj/411/02 ( Figure S3 and S4) may have reduced the protective efficacy of any pre-existing influenza antibodies (from prior infection or immunization by Mos/ 10/99-like viruses) before the inclusion of the Fuj/411/02 strain in the World Health Organization (WHO) recommendations for the seasonal influenza vaccine in 2004. Such a reduction in protective efficacy from the contemporary WHO influenza vaccine has indeed been suggested in several reports [14, 30, 31] . Similarly, although, the NA antigen is not usually specified in seasonal influenza vaccine, and its protective effect is unknown, its sequence variation in NA during this transitional period, may have also contributed to the reduced protection provided by the seasonal influenza A(H3N2) vaccine component during this period, when the Fuj/411/02-like viruses were emerging.