Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
AIDS Vaccines
/ immunology
Amino Acid Sequence
Animals
Antibodies, Neutralizing
/ chemistry
B-Lymphocytes
/ cytology
Crystallography, X-Ray
Female
HEK293 Cells
HIV Antibodies
/ chemistry
HIV-1
/ metabolism
Humans
Macaca mulatta
Male
Peptides
/ chemistry
Protein Structure, Tertiary
env Gene Products, Human Immunodeficiency Virus
/ chemistry
B cell ontogeny
HIV-1 vaccine
broadly neutralizing antibody
fusion peptide
immune monitoring
interaction hotspot
multidonor antibody class
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 07 2019
25 07 2019
Historique:
received:
31
01
2019
revised:
03
05
2019
accepted:
19
06
2019
entrez:
27
7
2019
pubmed:
28
7
2019
medline:
28
4
2020
Statut:
ppublish
Résumé
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
Identifiants
pubmed: 31348886
pii: S0092-8674(19)30733-0
doi: 10.1016/j.cell.2019.06.030
pmc: PMC6755680
mid: NIHMS1050005
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Neutralizing
0
HIV Antibodies
0
Peptides
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
567-584.e19Subventions
Organisme : NIAID NIH HHS
ID : R01 AI140891
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDA NIH HHS
ID : DP1 DA039543
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI138024
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120961
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103310
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AI999999
Pays : United States
Organisme : NIH HHS
ID : S10 OD020069
Pays : United States
Organisme : NIH HHS
ID : S10 OD019994
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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