Extended Heterosubtypic Neutralization and Preclinical Model In Vivo Protection from Clade 2.3.4.4b H5 Influenza...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Influenza virus causes significant global health and economic burdens, with up to 1 billion infections and 650,000 deaths annually.
• Current influenza vaccines, while effective, are limited by strain prediction and annual updates.
• The continuous threat of influenza epidemics and pandemics is highlighted by the H5N1 avian influenza outbreak affecting numerous mammalian species and humans.

Purpose of the Study:

• To evaluate the protective potential of two human monoclonal antibodies, PN-SIA28 and PN-SIA49, against diverse and recent influenza virus strains.
• To identify conserved epitopes targeted by broadly neutralizing antibodies for improved vaccine design.

Main Methods:

• Isolation of monoclonal antibodies (PN-SIA28, PN-SIA49) from a vaccinated individual.
• Assessment of antibody breadth, neutralization capacity, and in vivo protection against various influenza viruses, including pre-pandemic strains.
• Structural analysis to characterize antibody-antigen interactions and identify target epitopes.

Main Results:

• Both PN-SIA28 and PN-SIA49 demonstrated broad strain recognition and neutralization capabilities.
• The antibodies effectively neutralized pre-pandemic avian influenza viruses, including the H5N1 clade.
• Structural analysis revealed PN-SIA49 binds to a conserved HA stem region, a target of other broadly neutralizing antibodies.

Conclusions:

• Broadly neutralizing antibodies offer promising potential for developing universal influenza countermeasures against seasonal and pandemic strains.
• These findings provide valuable insights for designing targeted vaccine strategies to elicit broadly protective immune responses.
• The study supports the development of next-generation influenza vaccines aimed at conserved viral epitopes.