Abstract
Recent advances in high-throughput single cell sequencing have opened up new avenues into the investigation of B cell receptor (BCR) repertoires. In this study, PBMCs were collected from 17 human participants vaccinated with the split-inactivated influenza virus vaccine during the 2016-2017 influenza season. A combination of Immune Repertoire Capture (IRCTM) technology and IgG sequencing was performed on ~7,800 plasmablast (PB) cells and preferential IgG heavy-light chain pairings were investigated. In some participants, a single expanded clonotype accounted for ~22% of their PB BCR repertoire. Approximately 60% (10/17) of participants experienced convergent evolution, possessing public PBs that were elicited independently in multiple participants. Binding profiles of one private and three public PBs confirmed they were all subtype-specific, cross-reactive hemagglutinin (HA) head-directed antibodies. Collectively, this high-resolution antibody repertoire analysis demonstrated the impact evolution can have on BCRs in response to influenza virus vaccination, which can guide future universal influenza prophylactic approaches.
Highlights
Influenza virus is a highly contagious viral respiratory disease that causes hundreds of thousands of deaths and millions of hospitalizations every year [1]
Because probe staining can sometimes be a result of unspecific cell binding [37], we further enumerated the number of antibody secreting cells (ASC) against each of the four vaccine strains in the peripheral blood 7 days post-vaccination by Enzyme-linked immune absorbent spot (ELISpot) (Fig 1D)
Plasmablast repertoire analysis following influenza vaccination this report, a subset of 17 participants that had high serological changes and prominent PB expansion post-vaccination were selected in order to deeply characterize their PB response to influenza virus vaccination through single cell PB B cell receptor (BCR) sequencing
Summary
Influenza virus is a highly contagious viral respiratory disease that causes hundreds of thousands of deaths and millions of hospitalizations every year [1]. Annual vaccination is recommended to reduce influenza virus disease severity and limit transmission of the virus by eliciting antibodies that primarily target the hemagglutinin (HA) glycoprotein [2]. The antibody response elicited by the current seasonal influenza vaccine is predominantly strain-specific and highly dependent on pre-existing immunity and imprinting [3, 4]. How efficiently influenza virus vaccination recalls different pre-existing B cell memory responses in different participants and how they are correlated with protection needs further detailed.
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