Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses

Kathy Fernando, Haitao Hu, Houping Ni, James A. Hoxie, Drew Weissman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4+ T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4+ T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4+ T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design.

Original languageEnglish (US)
Pages (from-to)2538-2544
Number of pages7
JournalBlood
Volume109
Issue number6
DOIs
StatePublished - Mar 15 2007
Externally publishedYes

Fingerprint

T-cells
Viruses
Vaccines
Chemical activation
HIV
T-Lymphocytes
Antigen-Presenting Cells
Antigens
Viral Vaccines
CD4 Antigens
Immune system
Cell Communication
Virion
Viral DNA
Immune System
Lymph Nodes
Cell Proliferation
DNA
Infection

ASJC Scopus subject areas

  • Hematology

Cite this

Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses. / Fernando, Kathy; Hu, Haitao; Ni, Houping; Hoxie, James A.; Weissman, Drew.

In: Blood, Vol. 109, No. 6, 15.03.2007, p. 2538-2544.

Research output: Contribution to journalArticle

Fernando, Kathy ; Hu, Haitao ; Ni, Houping ; Hoxie, James A. ; Weissman, Drew. / Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses. In: Blood. 2007 ; Vol. 109, No. 6. pp. 2538-2544.
@article{4ee1a940372349babb20d8b349c00b61,
title = "Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses",
abstract = "The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4+ T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4+ T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4+ T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design.",
author = "Kathy Fernando and Haitao Hu and Houping Ni and Hoxie, {James A.} and Drew Weissman",
year = "2007",
month = "3",
day = "15",
doi = "10.1182/blood-2006-08-038661",
language = "English (US)",
volume = "109",
pages = "2538--2544",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses

AU - Fernando, Kathy

AU - Hu, Haitao

AU - Ni, Houping

AU - Hoxie, James A.

AU - Weissman, Drew

PY - 2007/3/15

Y1 - 2007/3/15

N2 - The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4+ T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4+ T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4+ T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design.

AB - The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4+ T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4+ T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4+ T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design.

UR - http://www.scopus.com/inward/record.url?scp=33947211449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947211449&partnerID=8YFLogxK

U2 - 10.1182/blood-2006-08-038661

DO - 10.1182/blood-2006-08-038661

M3 - Article

VL - 109

SP - 2538

EP - 2544

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -