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Series GSE135761 Query DataSets for GSE135761
Status Public on Aug 13, 2019
Title Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response Against Influenza Virus
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Antibodies display antigen-binding loops comprised of a hypervariable CDRH3 and V gene-encoded CDRs, where the latter may harbor gene-endowed or ‘public’ targeting solutions. To test this, we generated transgenic mice containing human CDRH3 diversity but simultaneously constrained to individual human immunoglobulin VH genes, including IGHV1-69, which shows biased usage in human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin stalk of Group 1 influenza A viruses. We then rank-ordered the VH-contribution to bnAb-epitope targeting following exposure to viral and nanoparticle displays of hemagglutinin. Notably, sequential immunization with a stalk-only hemagglutinin nanoparticle elicited Group 1 bnAbs, but only in IGHV1-69 constrained mice. This response required minimal affinity maturation, could be elicited under pre-existing influenza immunity, and when IGHV1-69 B cells were diluted to match the frequency measured in humans. Thus, encoded CDRs can naturally endow for specific antibody targets, and a rationally designed immunogen may elicit human influenza bnAbs through this principle.
Overall design Single cell and bulk BCR sequences from human IGHV1-69 restricted, human IGHV1-2 restricted, and WT C57BL/6 mice generated by deep sequencing using Illumina Miseq.
Contributor(s) Sangesland M, Kazer SW, Lingwood D
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Submission date Aug 12, 2019
Last update date Sep 24, 2019
Contact name Maya Sangesland
Organization name Ragon Institute of MGH, MIT, and Harvard
Lab Lingwood Lab
Street address 400 Technology Square
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (1475)
GSM4027730 BCR1__VH6901-A01_S97
GSM4027731 BCR1__VH6901-A02_S98
GSM4027732 BCR1__VH6901-A03_S99
BioProject PRJNA559930
SRA SRP218167

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE135761_Consensus_Alignments.txt.gz 37.4 Kb (ftp)(http) TXT
GSE135761_RAW.tar 83.7 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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