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 Blood, 15 March 2007, Vol. 109, No. 6, pp. 2538-2544.
Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-08-038661.

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IMMUNOBIOLOGY

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

Kathy Fernando1, Haitao Hu1, Houping Ni1, James A. Hoxie2, and Drew Weissman1

1 Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA; 2 Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA

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.


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H. Hu, K. Fernando, H. Ni, and D. Weissman
HIV Envelope Suppresses CD4+ T Cell Activation Independent of T Regulatory Cells
J. Immunol., April 15, 2008; 180(8): 5593 - 5600.
[Abstract] [Full Text] [PDF]


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