Hide and seek: interplay between influenza viruses and B cells

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Influenza virus hemagglutinin (HA) undergoes constant antigenic variation due to mutations and reassortment.
• Conserved HA epitopes exist, targeted by broadly protective antibodies, but are often hidden from immune surveillance.
• Current influenza vaccines primarily target variable epitopes, limiting broad protection against diverse strains.

Purpose of the Study:

• To characterize broadly protective antibodies targeting conserved influenza virus hemagglutinin (HA) epitopes.
• To understand viral strategies for evading immune responses against conserved epitopes.
• To identify strategies for activating B cells against these hidden HA epitopes for universal influenza vaccine development.

Main Methods:

• Analysis of the human B-cell antigen receptor (BCR) repertoire.
• Characterization of broadly protective antibodies and their targeted epitopes.
• Investigation of viral mechanisms, such as steric hindrance, that obscure conserved epitopes.

Main Results:

• Dissection of BCRs that recognize HA epitopes concealed within the native HA structure.
• Identification of broadly protective antibodies that target these hidden epitopes.
• Understanding of viral immune evasion strategies, including steric hindrance of conserved epitopes.

Conclusions:

• Broadly protective B cells can be activated against conserved, hidden HA epitopes.
• Strategies to overcome viral immune evasion are crucial for developing universal influenza vaccines.
• This research has implications for designing next-generation influenza vaccines offering broad and durable protection.