Influenza viruses are a constant threat to public health and significant measures have been taken to prepare for the potential emergence of a novel pandemic strain. However, seasonal vaccination has partial efficacy against drifted and novel strains, with the continued need for annual vaccination due to immune waning and antigenic drift for the vaccine to be updated to representative strains. Thus, there is a need for a universal influenza vaccine to more conserved antigen targets. Whilst the Influenza A viruses (IAV) haemagglutinin (HA) is highly variable between strains and subtypes, other proteins like the nucleoprotein (NP), non-structural proteins (NS) and polymerase acidic (PA) are more conserved and may provide cross-reactive immune mediated protection by vaccination. These alternate targets are currently under appreciated and may provide universal vaccine targets.
We utilized single IAV recombinant A/Puerto Rico/8/1934 (H1N1) proteins to immunize mice to decipher the contribution to protection of each influenza protein. Protective targets identified to enhance reduced viral load including the nucleoprotein, that could be incorporated to new vaccines due to high conservation with new influenza viruses to generate universal vaccines. Whilst the surface haemagglutinin (HA) provided the highest level of protection both from lethal infection, increased viral clearance, and remains our best target compared to others tested. To complement mouse studies, H1N1-specific antibody levels from pre- and post-infection human serum samples are being assessed to determine antigen specificity and viral loads and symptom severity.
Our study support the possibility of the existence of novel vaccine target in addition to the canonical HA proteins. It is worth to explore the other potential internal targets in other influenza viruses that can be used for the design of more effective and long-lasting vaccines.