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Are we getting close to development of a universal influenza vaccine?

Current influenza vaccines protect against influenza only when they match circulating strains. Development of a universal vaccine is of the highest public health importance. In a recent randomised, double-blinded study by Bernstein et al., 65 adult participants were selected and randomly assigned to one of five study groups. These included three prime-boost, chimeric haemagglutinin-based vaccine regimens and two placebo groups. Primary outcomes included reactogenicity and safety, while the secondary outcomes included immunogenicity and extended immunogenic response to phylogenetically distant strains. The adjuvanted inactivated vaccine, rather than the liveattenuated vaccine, produced a sevenfold increase in anti-H1 stalk antibody. Comparable antibody induction patterns were noted for H2, H9 and H18 which all belong to the phylogenetically distant group 1 of haemagglutinins. A similar increase in the live-attenuated vaccine was demonstrated only after receiving boost immunisation with adjuvanted inactivated vaccine. The experimental vaccines were well tolerated. The study had several limitations including lack of antibody persistence data, exclusion of children, and all participants demonstrated baseline antibodies to the haemagglutinin stalk prior to vaccination, likely induced by natural infection. This was the first proof-of-principle study to demonstrate that using a highly conserved influenza epitope can induce high serum titers of cross-reactive antibodies. These findings provide foundation and rationale for a development of a universal vaccine.