Abstract
Seasonal influenza vaccines have proven to be effective against well-matched viruses in healthy adults. However, rapid accumulation of mutations in the main antigenic surface proteins of influenza can compromise the efficiency of flu vaccines. Occasionally, influenza pandemics arise and present a different type of challenge to current seasonal vaccines. Novel vaccination strategies that can educate the host immune system to generate immune responses focusing on conserved epitopes on theses antigenic surface proteins are crucial for controlling and limiting influenza epidemics and pandemics. In this study, we have sequentially vaccinated mice with heterosubtypic influenza HA virus-like particles (VLPs) harboring H1, H8, and H13 from the HA phylogenetic group 1, or H3, H4, and H10 from the HA phylogenetic group 2, or in various combinations. The immunized animals were fully protected when challenged with lethal doses of heterosubtypic viruses from either phylogenetic group. Our vaccination approach demonstrates a promising strategy for the development of a ‘universal influenza vaccine’.
Highlights
Seasonal influenza epidemics and occasional pandemics remain a public health concern throughout the world
While broadly neutralizing antibodies are ideal for protective immunity and the generation of such antibodies could result in universal protection, they are rare and difficult to produce via vaccination
TEM data showed that the prepared virus-like particles (VLPs) were spherical in morphology with a diameter of ∼100 nm (Fig. 1C), which was similar with previous studies[16,17]
Summary
Seasonal influenza epidemics and occasional pandemics remain a public health concern throughout the world. Successive infections with live viruses lead to a reduction in strain-specific antibody titers against the most recent strain while nurturing broader epitope-specific antibody titers[4,11,12,13]. Designs and iterative antigenic exposure provide important novel insights into the development of immune responses for creating a successful ‘universal influenza vaccine’. These observations strongly suggest that sequential infections or vaccinations play a central role in the induction of broadly cross-reactive antibodies. We have designed a cross-subtypic sequential vaccination strategy with different subtypic influenza virus-like particles (VLPs) containing HA from H1N1, H8N4, H13N6 (HA phylogenetic group 1) or H3N2, H4N6, and H10N2 (HA phylogenetic group 2) viral strains or in combination, to elicit broad protection against divergent viruses in the same HA phylogenetic group or both groups
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