Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin.

Abstract:

:Vaccine-induced memory B cell responses to evolving viruses like influenza A involve activation of pre-existing immunity and generation of new responses. To define the contribution of these two types of responses, we analyzed the response to H7N9 vaccination in H7N9-naive adults. We performed comprehensive comparisons at the single-cell level of the kinetics, Ig repertoire, and activation phenotype of established pre-existing memory B cells recognizing conserved epitopes and the newly generated memory B cells directed toward H7 strain-specific epitopes. The recall response to conserved epitopes on H7 HA involved a transient expansion of memory B cells with little observed adaptation. However, the B cell response to newly encountered epitopes was phenotypically distinct and generated a sustained memory population that evolved and affinity matured months after vaccination. These findings establish clear differences between newly generated and pre-existing memory B cells, highlighting the challenges in achieving long-lasting, broad protection against an ever-evolving virus.

journal_name

Immunity

journal_title

Immunity

authors

Andrews SF,Chambers MJ,Schramm CA,Plyler J,Raab JE,Kanekiyo M,Gillespie RA,Ransier A,Darko S,Hu J,Chen X,Yassine HM,Boyington JC,Crank MC,Chen GL,Coates E,Mascola JR,Douek DC,Graham BS,Ledgerwood JE,McDermott AB

doi

10.1016/j.immuni.2019.06.024

subject

Has Abstract

pub_date

2019-08-20 00:00:00

pages

398-410.e5

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(19)30294-8

journal_volume

51

pub_type

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