Immunogen selection and prior immunity shape antibody breadth following immunisation with avian H5 hemagglutinin

Avian influenza A viruses pose a constant risk to humans due to their ability to infect multiple species and high mortality rates. Specific strains from the H5 subtype, particularly the 2.3.4.4b clade, have been discovered in over 60 mammalian species, sparking concerns about potential pandemics. To improve vaccine design and pandemic readiness, researchers studied how different H5 strains are recognized by the immune system.

They examined neutralizing antibody responses in C57BL/6 mice after exposure to adjuvanted recombinant HA protein vaccines derived from genetically diverse H5 human isolates collected between 2003 and 2023. By assessing neutralisation activity against seven H5 HA variants using pseudotyped viruses and a PR8-reassortant virus, the study revealed significant cross-strain neutralisation variability.

Conventional vaccines based on the A/Indonesia/05/2005 strain showed limited activity against emerging clade 2.3.4.4b viruses, while ancestral variants demonstrated broader cross-neutralisation capabilities but with reduced potency. Formulations containing polyvalent H5 HA proteins and nanoparticles displaying H5 HA showed increased cross-neutralisation against diverse H5 strains.

The study also investigated the influence of prior immunity on H5 vaccine immunogenicity in mouse models. Mice primed with either seasonal influenza infection or a quadrivalent influenza vaccine (QIV) prior to H5 HA immunisation showed enhanced neutralizing responses against A/Fujian-Sanyuan/21099/2017 (clade 2.3.4.4b) H5. The findings collectively demonstrate that the choice of immunogens and existing immunity significantly impact antibody breadth following immunisation with avian A(H5) hemagglutinin.