Engineering an Antibody V Gene-Selective Vaccine

The ligand-binding surface of the B cell receptor (BCR) is formed by encoded and non-encoded antigen complementarity determining regions (CDRs). Genetically reproducible or ‘public’ antibodies can arise when the encoded CDRs play deterministic roles in antigen recognition, notably within human broad...

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Main Authors:	Larance Ronsard, Ashraf S. Yousif, Julianne Peabody, Vintus Okonkwo, Pascal Devant, Alemu Tekewe Mogus, Ralston M. Barnes, Daniel Rohrer, Nils Lonberg, David Peabody, Bryce Chackerian, Daniel Lingwood
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2021-09-01
Series:	Frontiers in Immunology
Subjects:	antibody B cell receptor lineage VLP prime
Online Access:	https://www.frontiersin.org/articles/10.3389/fimmu.2021.730471/full

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spelling	doaj-c501fb4e290e4b8e90012f7b9a25ca182021-09-09T14:13:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.730471730471Engineering an Antibody V Gene-Selective VaccineLarance Ronsard0Ashraf S. Yousif1Julianne Peabody2Vintus Okonkwo3Pascal Devant4Alemu Tekewe Mogus5Ralston M. Barnes6Daniel Rohrer7Nils Lonberg8David Peabody9Bryce Chackerian10Daniel Lingwood11The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United StatesThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United StatesDepartment of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, United StatesThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United StatesThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United StatesDepartment of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, United StatesBristol-Myers Squibb, Redwood City, CA, United StatesBristol-Myers Squibb, Redwood City, CA, United StatesBristol-Myers Squibb, Redwood City, CA, United StatesDepartment of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, United StatesDepartment of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, United StatesThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United StatesThe ligand-binding surface of the B cell receptor (BCR) is formed by encoded and non-encoded antigen complementarity determining regions (CDRs). Genetically reproducible or ‘public’ antibodies can arise when the encoded CDRs play deterministic roles in antigen recognition, notably within human broadly neutralizing antibodies against HIV and influenza virus. We sought to exploit this by engineering virus-like-particle (VLP) vaccines that harbor multivalent affinity against gene-encoded moieties of the BCR antigen binding site. As proof of concept, we deployed a library of RNA bacteriophage VLPs displaying random peptides to identify a multivalent antigen that selectively triggered germline BCRs using the human VH gene IGVH1-202. This VLP selectively primed IGHV1-202 BCRs that were present within a highly diversified germline antibody repertoire within humanized mice. Our approach thus provides methodology to generate antigens that engage specific BCR configurations of interest, in the absence of structure-based information.https://www.frontiersin.org/articles/10.3389/fimmu.2021.730471/fullantibodyB cell receptorlineageVLPprime
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Larance Ronsard Ashraf S. Yousif Julianne Peabody Vintus Okonkwo Pascal Devant Alemu Tekewe Mogus Ralston M. Barnes Daniel Rohrer Nils Lonberg David Peabody Bryce Chackerian Daniel Lingwood
spellingShingle	Larance Ronsard Ashraf S. Yousif Julianne Peabody Vintus Okonkwo Pascal Devant Alemu Tekewe Mogus Ralston M. Barnes Daniel Rohrer Nils Lonberg David Peabody Bryce Chackerian Daniel Lingwood Engineering an Antibody V Gene-Selective Vaccine Frontiers in Immunology antibody B cell receptor lineage VLP prime
author_facet	Larance Ronsard Ashraf S. Yousif Julianne Peabody Vintus Okonkwo Pascal Devant Alemu Tekewe Mogus Ralston M. Barnes Daniel Rohrer Nils Lonberg David Peabody Bryce Chackerian Daniel Lingwood
author_sort	Larance Ronsard
title	Engineering an Antibody V Gene-Selective Vaccine
title_short	Engineering an Antibody V Gene-Selective Vaccine
title_full	Engineering an Antibody V Gene-Selective Vaccine
title_fullStr	Engineering an Antibody V Gene-Selective Vaccine
title_full_unstemmed	Engineering an Antibody V Gene-Selective Vaccine
title_sort	engineering an antibody v gene-selective vaccine
publisher	Frontiers Media S.A.
series	Frontiers in Immunology
issn	1664-3224
publishDate	2021-09-01
description	The ligand-binding surface of the B cell receptor (BCR) is formed by encoded and non-encoded antigen complementarity determining regions (CDRs). Genetically reproducible or ‘public’ antibodies can arise when the encoded CDRs play deterministic roles in antigen recognition, notably within human broadly neutralizing antibodies against HIV and influenza virus. We sought to exploit this by engineering virus-like-particle (VLP) vaccines that harbor multivalent affinity against gene-encoded moieties of the BCR antigen binding site. As proof of concept, we deployed a library of RNA bacteriophage VLPs displaying random peptides to identify a multivalent antigen that selectively triggered germline BCRs using the human VH gene IGVH1-202. This VLP selectively primed IGHV1-202 BCRs that were present within a highly diversified germline antibody repertoire within humanized mice. Our approach thus provides methodology to generate antigens that engage specific BCR configurations of interest, in the absence of structure-based information.
topic	antibody B cell receptor lineage VLP prime
url	https://www.frontiersin.org/articles/10.3389/fimmu.2021.730471/full
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Engineering an Antibody V Gene-Selective Vaccine

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