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Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response Against Influenza Virus

ABSTRACT: Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response Against Influenza Virus

PROVIDER: PRJNA559930 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9957300_1.fastq.gz	Fastqsanger.gz
	SRR9957300_2.fastq.gz	Fastqsanger.gz
	SRR9957310_1.fastq.gz	Fastqsanger.gz
	SRR9957310_2.fastq.gz	Fastqsanger.gz
	SRR9957320_1.fastq.gz	Fastqsanger.gz

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Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response Against Influenza Virus

Project description: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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