Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis.

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Vaccine-induced B cells differentiate into follicular or extrafollicular pathways, with the latter rapidly producing antibodies.
• Rabies virus (RABV) postexposure prophylaxis (PEP) requires swift humoral immunity for protection.
• Current RABV PEP is costly and resource-intensive, necessitating more rapid and effective vaccines.

Purpose of the Study:

• To investigate if targeting the extrafollicular B cell pathway can enhance the speed and magnitude of RABV PEP.
• To construct and characterize a recombinant RABV vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF).

Main Methods:

• Developed a recombinant RABV vaccine expressing BAFF (rRABV-mBAFF).
• Assessed antibody response kinetics and magnitude in mice post-vaccination.
• Evaluated survivorship in PEP settings and used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model to confirm pathway modulation.

Main Results:

• rRABV-mBAFF induced a faster and higher antibody response compared to the control RABV vaccine.
• The modified vaccine enhanced survivorship in PEP settings.
• Experiments in SAP-deficient mice confirmed that BAFF primarily augmented the extrafollicular B cell pathway, not the germinal center pathway.

Conclusions:

• Targeting the extrafollicular B cell pathway with rRABV-mBAFF accelerates protective antibody generation for RABV PEP.
• This strategy offers a potential pathway towards a single-dose RABV vaccine, simplifying current PEP protocols.
• Manipulating B cell activation pathways may improve vaccine efficacy against other pathogens requiring rapid immune responses.