Influenza virus geometry shapes the immune response against it

Influenza surface glycoprotein – Hemagglutinin (HA) is the main target of the immune system following exposure to the virus. Most antibodies elicited following vaccination or infection are created against the head, which is highly mutable. A vaccination approach that would target immune response towards evolutionarily conserved residues on hemagglutinin stem can elicit broadly neutralizing antibodies capable of fighting many flu strains.

Using mice experiments, in-silico models of designed immunogens (nanoparticles) and of antibody development against flu, we study how a targeted response against conserved stem residues can be elicited. We find that because of the high density of HA molecules on the virus, infection by the virus drives the proliferation of B cells targeting mutable residues while suppressing those targeting conserved sites. Strong response against the conserved residue can be achieved by vaccinating with nanoparticles presenting the stem part of HA alone, of flu strain different from those to which the system was already exposed to.