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Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens? / Klasse, P. J.; Ozorowski, Gabriel; Sanders, Rogier W. et al.

In: Cell host & microbe, Vol. 27, No. 4, 08.04.2020, p. 507-518.

Research output: Contribution to journalReview articleAcademicpeer-review

Harvard

Klasse, PJ, Ozorowski, G, Sanders, RW & Moore, JP 2020, 'Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?', Cell host & microbe, vol. 27, no. 4, pp. 507-518. https://doi.org/10.1016/j.chom.2020.03.018

APA

Klasse, P. J., Ozorowski, G., Sanders, R. W., & Moore, J. P. (2020). Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens? Cell host & microbe, 27(4), 507-518. https://doi.org/10.1016/j.chom.2020.03.018

Vancouver

Author

Klasse, P. J. ; Ozorowski, Gabriel ; Sanders, Rogier W. et al. / Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?. In: Cell host & microbe. 2020 ; Vol. 27, No. 4. pp. 507-518.

BibTeX

@article{cc938f3118ff4a0cbbed7002b1f46dc5,
title = "Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?",
abstract = "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.",
keywords = "CD4, HIV-1, HIV-1 Env trimers, adaptive immunity, envelope glycoprotein, innate immunity, mannose glycans, nanoparticles, neutralizing Abs, vaccine",
author = "Klasse, {P. J.} and Gabriel Ozorowski and Sanders, {Rogier W.} and Moore, {John P.}",
year = "2020",
month = apr,
day = "8",
doi = "10.1016/j.chom.2020.03.018",
language = "English",
volume = "27",
pages = "507--518",
journal = "Cell host & microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?

AU - Klasse, P. J.

AU - Ozorowski, Gabriel

AU - Sanders, Rogier W.

AU - Moore, John P.

PY - 2020/4/8

Y1 - 2020/4/8

N2 - 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.

AB - 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.

KW - CD4

KW - HIV-1

KW - HIV-1 Env trimers

KW - adaptive immunity

KW - envelope glycoprotein

KW - innate immunity

KW - mannose glycans

KW - nanoparticles

KW - neutralizing Abs

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85082736583&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2020.03.018

DO - 10.1016/j.chom.2020.03.018

M3 - Review article

C2 - 32272076

VL - 27

SP - 507

EP - 518

JO - Cell host & microbe

JF - Cell host & microbe

SN - 1931-3128

IS - 4

ER -

ID: 11336699