Targeting RSV-neutralizing B cell receptors with anti-idiotypic antibodies

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections, particularly in infants and older adults.
• Current infant protection against RSV relies on passive immunity, highlighting the need for a direct infant vaccine.
• Specific antibody gene pairings (VH3-21/VL1-40) neutralize RSV without affinity maturation, presenting an attractive vaccination target.

Purpose of the Study:

• To develop a novel vaccine immunogen targeting B cells specific for a conserved, neutralizing antibody precursor.
• To evaluate the efficacy of an anti-idiotypic monoclonal antibody (ai-mAb) in engaging target B cells without activating off-target cells.

Main Methods:

• Development of an anti-idiotypic monoclonal antibody (ai-mAb) immunogen.
• Characterization of ai-mAb specificity for unmutated VH3-21/VL1-40 B cell receptors (BCRs).
• Assessment of B cell engagement and activation by the ai-mAb compared to recombinant pre-fusion (preF) protein.

Main Results:

• The ai-mAb specifically targets B cells expressing unmutated VH3-21/VL1-40 BCRs.
• The ai-mAb efficiently engages B cells with the desired target BCRs.
• Unlike preF vaccines, the ai-mAb avoids activation of off-target, non-neutralizing B cells.

Conclusions:

• An ai-mAb-based immunogen demonstrates proof of concept for a new RSV vaccine strategy.
• This approach can target B cells predisposed to producing broadly neutralizing RSV antibodies.
• This method offers a potential pathway for developing rapid, effective infant RSV vaccines.