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A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.
- Source :
-
Science (New York, N.Y.) [Science] 2019 Dec 06; Vol. 366 (6470). Date of Electronic Publication: 2019 Oct 31. - Publication Year :
- 2019
-
Abstract
- Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.<br /> (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Adoptive Transfer
Amino Acid Sequence
Animals
B-Lymphocytes immunology
Broadly Neutralizing Antibodies chemistry
Complementarity Determining Regions immunology
Disease Models, Animal
HEK293 Cells
HIV Antibodies chemistry
Humans
Mice
Mice, Knockout
Precursor Cells, B-Lymphoid immunology
AIDS Vaccines genetics
AIDS Vaccines immunology
Broadly Neutralizing Antibodies immunology
Directed Molecular Evolution methods
HIV Antibodies immunology
Immunogenicity, Vaccine
env Gene Products, Human Immunodeficiency Virus genetics
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 366
- Issue :
- 6470
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 31672916
- Full Text :
- https://doi.org/10.1126/science.aax4380