Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.
AIDS Vaccines
/ immunology
Antigen Presentation
/ genetics
HIV Antibodies
/ immunology
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Immunization
Immunoglobulin A
/ blood
Immunoglobulin G
/ blood
Interferon Regulatory Factor-7
/ metabolism
Interferon Type I
/ immunology
Interferon-gamma
/ immunology
Mechanistic Target of Rapamycin Complex 1
/ genetics
NF-kappa B
/ metabolism
Placebos
/ administration & dosage
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:
20 02 2019
20 02 2019
Historique:
received:
23
01
2018
accepted:
25
01
2019
entrez:
22
2
2019
pubmed:
23
2
2019
medline:
4
4
2019
Statut:
epublish
Résumé
The RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the transcriptomic profile of blood collected from 223 participants and 40 placebo recipients. Pathway-level analysis of HIV-1 negative vaccinees reveals that type I interferons that activate the IRF7 antiviral program and type II interferon-stimulated genes implicated in antigen-presentation are both associated with a reduced risk of HIV-1 acquisition. In contrast, genes upstream and downstream of NF-κB, mTORC1 and host genes required for viral infection are associated with an increased risk of HIV-1 acquisition among vaccinees and placebo recipients, defining a vaccine independent association with HIV-1 acquisition. Our transcriptomic analysis of RV144 trial samples identifies IRF7 as a mediator of protection and the activation of mTORC1 as a correlate of the risk of HIV-1 acquisition.
Identifiants
pubmed: 30787294
doi: 10.1038/s41467-019-08854-2
pii: 10.1038/s41467-019-08854-2
pmc: PMC6382801
doi:
Substances chimiques
AIDS Vaccines
0
HIV Antibodies
0
IRF7 protein, human
0
Immunoglobulin A
0
Immunoglobulin G
0
Interferon Regulatory Factor-7
0
Interferon Type I
0
NF-kappa B
0
Placebos
0
env Gene Products, Human Immunodeficiency Virus
0
Interferon-gamma
82115-62-6
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
863Subventions
Organisme : NIAID NIH HHS
ID : P30 AI064518
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068618
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
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