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Vaccine . Influenza vaccination-induced H3 stalk-reactive memory B-cell clone expansion

tetano

Editor, Senior Moderator
Vaccine


. 2023 Jan 6;S0264-410X(22)01603-6.
doi: 10.1016/j.vaccine.2022.12.068. Online ahead of print.
Influenza vaccination-induced H3 stalk-reactive memory B-cell clone expansion


Zhaoyi Long[SUP] 1 [/SUP], Jiang He[SUP] 2 [/SUP], Qinglu Shuai[SUP] 1 [/SUP], Ke Zhang[SUP] 3 [/SUP], Jim Xiang[SUP] 4 [/SUP], Huan Wang[SUP] 5 [/SUP], Shuang Xie[SUP] 1 [/SUP], Shengyu Wang[SUP] 5 [/SUP], Wensheng Du[SUP] 3 [/SUP], Xinsheng Yao[SUP] 6 [/SUP], Junqiong Huang[SUP] 7 [/SUP]



Affiliations

Abstract

Current vaccine formulations elicit a recall immune response against viruses by targeting epitopes on the globular head of hemagglutinin (HA), and stalk-reactive antibodies are rarely found. However, stalk-specific memory B-cell expansion after influenza vaccination is poorly understood. In this study, B cells were isolated from individuals immunized with seasonal tetravalent influenza vaccines at days 0 and 28 for H7N9 stimulation in vitro. Plasma and supernatants were collected for the analysis of anti-HA IgG using ELISA and a Luminex assay. Memory B cells were positively enriched, and total RNA was extracted for B cell receptor (BCR) H-CDR3 sequencing. All subjects displayed increased anti-H3 antibody secretion after vaccination, whereas no increase in cH5/3-reactive IgG levels was detected. The number of shared memory B-cell clones among individuals dropped dramatically from 593 to 37. Four out of 5 subjects displayed enhanced frequencies of the VH3-23 and VH3-30 genes, and one exhibited an increase in the frequency of VH1-18, which are associated with the stalk of HA. An increase in H3 stalk-specific antibodies produced by B cells stimulated with H7N9 viruses was detected after vaccination. These results demonstrated that H3 stalk-specific memory B cells can expand and secrete antibodies that bind to the stalk in vitro, although no increase in serum H3 stalk-reactive antibodies was found after vaccination, indicating potential for developing a universal vaccine strategy.

Keywords: CDR3; HA Stalk; Influenza; Memory B Cells; Vaccine.
 
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