A universal influenza vaccine
Influenza A virus (IAV) variants are subtyped on the basis of heterogeneity of the viral surface proteins haemagglutinin (HA) and neuraminidase (NA), which comprise the major targets for natural host immunity. However, due to the continual accumulation of amino acid changes, known as antigenic drift, immunity to one IAV strain does not protect against other strains. Importantly, some animals such as birds and swine can be infected with IAV and through re-assortment can lead to new strains of IAV capable of infecting humans. Given that man has no natural immunity against these novel strains, they can cause pandemics, which may be associated with very high mortality rates. The EU-funded FLUTCORE project was designed to address the challenge of IAV vaccine development by overcoming the limitations of existing vaccines. The rationale was to generate a vaccine capable of inducing protective immunity against many strains of influenza. This necessitates the targeting of viral proteins that are conserved between the major IAV strains responsible for seasonal influenza. In this context, researchers investigated conserved regions of important IAV proteins that could be targeted by protective immune responses. Inherently, well conserved sequences are poor immunogens. So, FLUTCORE had to present those IAV antigens to the immune system in such a way that they elicit vigorous and protective immune responses. For this purpose, project partners exploited virus-like particles (VLPs), protein complexes that mimic infectious virions but lack the genetic material to replicate. VLPs not only elicit immune responses but they can be genetically manipulated to present any desired antigen, comprising well-recognised tools for vaccine development. FLUTCORE identified conserved epitopes in HA and in the matrix protein and genetically engineered these antigens into hepatitis B VLPs. Following purification, the most immunogenic VLPs were validated in pre-clinical mouse models against IAV infection. Overall, the FLUTCORE project provided an innovative means of developing an effective vaccine that could provide immunity against most pathogenic IAV strains. The next step is to test the lead vaccine for safety and efficacy in the clinic.
Keywords
Influenza, vaccine, haemagglutinin, FLUTCORE, VLP
