Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?
AIDS Vaccines
/ immunology
Adaptive Immunity
Antibodies, Neutralizing
/ immunology
B-Lymphocytes
/ immunology
CD4 Antigens
/ immunology
Epitopes, B-Lymphocyte
/ immunology
HIV Antibodies
/ chemistry
HIV-1
/ chemistry
Immunity, Innate
Mannose
/ chemistry
Membrane Glycoproteins
/ chemistry
Molecular Mimicry
Protein Binding
Protein Multimerization
T-Lymphocytes
/ immunology
env Gene Products, Human Immunodeficiency Virus
/ immunology
CD4
HIV-1
HIV-1 Env trimers
adaptive immunity
envelope glycoprotein
innate immunity
mannose glycans
nanoparticles
neutralizing Abs
vaccine
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
23
02
2020
revised:
17
03
2020
accepted:
22
03
2020
entrez:
10
4
2020
pubmed:
10
4
2020
medline:
30
12
2020
Statut:
ppublish
Résumé
Recombinant HIV-1 envelope (Env) glycoproteins of ever-increasing sophistication have been evaluated as vaccine candidates for over 30 years. Structurally defined mimics of native trimeric Env glycoproteins (e.g., SOSIP trimers) present multiple epitopes for broadly neutralizing antibodies (bNAbs) and their germline precursors, but elicitation of bNAbs remains elusive. Here, we argue that the interactions between Env and the immune system render it exceptional among viral vaccine antigens and hinder its immunogenicity in absolute and comparative terms. In other words, Env binds to CD4 on key immune cells and transduces signals that can compromise their function. Moreover, the extensive array of oligomannose glycans on Env shields peptidic B cell epitopes, impedes the presentation of T helper cell epitopes, and attracts mannose binding proteins, which could affect the antibody response. We suggest lines of research for assessing how to overcome obstacles that the exceptional features of Env impose on the creation of a successful HIV-1 vaccine.
Identifiants
pubmed: 32272076
pii: S1931-3128(20)30182-7
doi: 10.1016/j.chom.2020.03.018
pmc: PMC7187920
mid: NIHMS1581715
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Neutralizing
0
CD4 Antigens
0
Epitopes, B-Lymphocyte
0
HIV Antibodies
0
Membrane Glycoproteins
0
env Gene Products, Human Immunodeficiency Virus
0
Mannose
PHA4727WTP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
507-518Subventions
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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