FIG 4.

FRA. FRA neutralizing titers were determined for each group of immunologically naive ferrets (n = 4) vaccinated two times (days 84 and 168) with one of the four COBRA H3N3 VLP vaccines (T6, T7, T10, or T11) or H3N3 VLP vaccines expressing wild-type HA proteins from Wisc/05 or TX/12. At day 182, sera were collected and tested in an FRA against four H3N2 viruses isolated between 2012 and 2016 representing clades 3c.1 (TX/12) (A and I), 3c.3a (Switz/13) (B and J), 3c.2a (HK/14) (C and K), and 3c.2a1 (Sing/16) (D and L). Alternatively, ferrets were infected with wild-type H3N2 influenza viruses (Pan/99, Wisc/05, or TX/12), and sera collected at day 182 postinfection were also tested in an FRA assay against the four H3N2 viruses (A to D). Ferrets infected with Pan/99 were also subsequently vaccinated with H3N3 VLPs expressing one of four COBRA H3 HA antigens or the Wisc/05 or TX/12 wild-type HA proteins. Collected sera was assayed against the four H3N2 viruses (I to L). For each virus, the virus concentration was standardized to 1.2 × 10⁴ FFU/ml. The dotted lines represent the 50% inhibition and the 80% inhibition of viral infection by antisera compared to virus-only control wells (A to D and I to L). A heat map of the log₂ serum dilution titer for the 50 and 80% inhibition per virus for each group of ferrets (E to H and M to P) was also generated. Colors range from white (lowest level of inhibition) to dark blue (highest level of inhibition).