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| 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
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| 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.
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| 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.
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| Contributor(s) |
Sangesland M, Kazer SW, Lingwood D |
| Citation missing |
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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 |
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| Platforms (1) |
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| Samples (1475)
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| Relations |
| BioProject |
PRJNA559930 |
| SRA |
SRP218167 |
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