Mice immunized with N1 neuraminidase in a single cycle infectious virus or in a recombinant nanoparticle vaccine are protected against lethal challenge with highly pathogenic avian influenza H5N1 influenza

Recent spillover of highly pathogenic H5N1 avian influenza into various mammalian species has raised concerns. Rapidly synthesizable vaccine candidates are crucial in protecting humans against emerging pathogens. Researchers have investigated two vaccine candidates: a pH1N1 virus lacking hemagglutinin (HA) that limits infection to a single cycle (sciIAV) and Cobalt lipid-porphyrin nanoparticles decorated with neuraminidase of HPAI H5N1 (N1-CoPoP).

Intranasal inoculation of C57BL/6 mice with a single dose of pH1N1 sciIAV did not result in increased serum NA antibodies compared to uninoculated mice. However, intramuscular inoculation with the N1-CoPoP alone or in combination with pH1N1 sciIAV led to increased N1 IgG antibodies. When challenged with HPAIV H5N1, all mice given either pH1N1 sciIAV or N1-CoPoP were protected against weight loss, unlike unvaccinated mice that suffered significant body weight loss and succumbed to viral infection between 7 and 10 days post-infection (dpi).

Both pH1N1 sciIAV and N1-CoPoP immunization minimized viral infection, with only one mouse receiving pH1N1 sciIAV showing detectable viral titer in the lungs at 4 days post-infection (dpi). By 6 dpi, no mouse inoculated with either vaccine had detectable virus in nasal turbinates, lungs, or the brain, while uninoculated mice displayed high viral titers in all three. Both vaccine candidates proved protective and warrant further investigation as potential alternatives for future influenza outbreaks.