Submitted August 1, 2006
Accepted October 5, 2006
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, and Drew Weissman*
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States
* Corresponding author; email: dreww{at}mail.med.upenn.edu.
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 co-receptors. Env is commonly employed 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.
