Terminally Differentiated Influenza-Specific Effector Memory B Cells Circulate after Live Attenuated Influenza...

Area of Science:

• Immunology
• Vaccinology
• Cellular immunology

Background:

• Live attenuated influenza vaccination (LAIV) is the sole FDA-approved mucosal influenza vaccine.
• Circulating correlates of protection for LAIV are currently lacking.
• Previous studies identified HA-specific IgD-negative memory B cells predicting responses after inactivated influenza vaccine (IIV).

Purpose of the Study:

• To profile circulating HA-specific IgD-negative memory B cells following LAIV.
• To identify circulating B cell subsets that predict antibody responses after LAIV.
• To compare B cell responses induced by LAIV versus IIV.

Main Methods:

• Analysis of circulating HA-specific IgD-negative memory B cells in patients after LAIV.
• Phenotypic and transcriptional profiling using fluorochrome-labeled hemagglutinin (HA) antigen.
• Supervised and unsupervised analyses to identify cell subsets and correlate with antibody responses.

Main Results:

• LAIV induces circulating T-bet-positive HA-specific IgD-negative B cells, phenotypically similar to those after IIV.
• The magnitude of these T-bet-positive cells did not correlate with systemic HA-IgG responses after LAIV.
• LAIV preferentially induced HA-specific IgD-negative B cells co-expressing TBX21 and Zeb2, indicating terminal differentiation.
• LAIV-induced T-bet-positive B cells could not be recalled as antibody-secreting cells upon re-challenge.

Conclusions:

• Circulating HA-specific IgD-negative B cell responses differ between LAIV and IIV platforms.
• LAIV induces terminally differentiated B cells that do not predict antibody levels or recall responses.
• Novel circulating B cell markers correlating with LAIV efficacy remain to be identified.