Immune checkpoint modulation enhances HIV-1 antibody induction.
AIDS Vaccines
/ administration & dosage
Animals
Antibodies, Blocking
/ administration & dosage
Antibodies, Neutralizing
/ blood
B-Lymphocytes
/ immunology
CD4 Antigens
/ genetics
CTLA-4 Antigen
/ antagonists & inhibitors
HIV Antibodies
/ blood
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Immunologic Factors
/ administration & dosage
Lymphocyte Activation
Macaca mulatta
/ immunology
Mice
Mice, Transgenic
Receptors, OX40
/ agonists
T-Lymphocytes, Helper-Inducer
/ immunology
Transcriptome
Vaccination
/ methods
env Gene Products, Human Immunodeficiency Virus
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 02 2020
19 02 2020
Historique:
received:
19
07
2019
accepted:
27
01
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
30
4
2020
Statut:
epublish
Résumé
Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses.
Identifiants
pubmed: 32075963
doi: 10.1038/s41467-020-14670-w
pii: 10.1038/s41467-020-14670-w
pmc: PMC7031230
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Blocking
0
Antibodies, Neutralizing
0
CD4 Antigens
0
CTLA-4 Antigen
0
HIV Antibodies
0
Immunologic Factors
0
Receptors, OX40
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
948Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI100645
Pays : United States
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/K012037
Pays : International
Organisme : Medical Research Council
ID : MR/K012037/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144371
Pays : United States
Organisme : NIH HHS
ID : P40 OD012217
Pays : United States
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