Seasonal and pandemic influenza virus infections can cause significant disease worldwide. Current vaccines only provide limited, short-lived protection, and antigenic drift/shift in the hemagglutinin (HA) surface glycoprotein necessitates their annual reformulation and re-administration. To overcome these limitations, universal influenza virus vaccine strategies aim at eliciting broadly protective antibodies to conserved epitopes of the HA. We have developed ‘chimeric’ HA constructs which retain the conserved stalk domain of the HA and have exotic HA heads. Vaccination and boosting with such constructs successfully redirects the immune system in animals and in humans towards the conserved immune sub-dominant domains of the HA stalks resulting in an antigenic silencing of the HA heads and a protective immune response facilitated by the conserved HA stalks. In mice and ferrets such a strategy protects the animals against challenge with different influenza A strains as well as against different influenza B variants. Although phase I trials have been successfully conducted, further extensive trials will be necessary in the future in order to make this ‘chimeric’ HA approach an FDA-approved vaccine.

Learning Objectives:

1. Why is antigenic drift/shift responsible for the occasional very low efficacy of influenza virus vaccines and why is the composition of influenza virus vaccines adjusted on an annual basis?

2. Why are other vaccines not altered on an annual basis and why can they be used effectively over many decades? What is the principle behind the approach to develop a universal influenza virus vaccine?

3. Why is the technology of reverse genetics instrumental in making safe and protective universal influenza virus vaccines?