Human Dendritic Cells Transduced with Herpes Simplex Virus Amplicons Encoding Human Immunodeficiency Virus Type 1 (HIV-1) gp120 Elicit Adaptive Immune Responses from Human Cells Engrafted into NOD/SCID Mice and Confer Partial Protection against HIV-1 Challenge

Authors

• Santhi Gorantla, University of Nebraska Medical Center
• Kathlyn Santos, University of Rochester Medical Center
• VaKara Meyer, University of Nebraska Medical Center
• Stephen Dewhurst, University of Rochester Medical Center
• William J. Bowers, University of Rochester Medical Center
• Howard J. Federoff, University of Rochester Medical Center
• Howard Gendelman, University of Nebraska Medical Center & Nebraska Center for VirologyFollow
• Larisa Poluektova, University of Nebraska Medical Center

Document Type

Article

Date of this Version

February 2005

Comments

Published in JOURNAL OF VIROLOGY, Feb. 2005, p. 2124–2132 Vol. 79, No. 4 0022-538X doi:10.1128/JVI.79.4.2124–2132.2005 Copyright © 2005, American Society for Microbiology. Used by permission.

Abstract

Small-animal models are needed to test human immunodeficiency virus (HIV) vaccine efficacy following viral challenge. To this end, we examined HIV-1-specific immune responses following immunization of nonobese diabetic-severe combined immunodeficient mice that were repopulated with human peripheral blood lymphocytes (hu-PBL-NOD/SCID mice). Autologous dendritic cells (DC) were transduced ex vivo with replicationdefective, helper virus-free, herpes simplex virus type 1 (HSV-1) amplicons that expressed HIV-1 gp120 and were then injected into the hu-PBL-NOD/SCID mice. This resulted in primary HIV-1-specific humoral and cellular immune responses. Serum samples from vaccinated animals contained human immunoglobulin G that reacted with HIV-1 Env proteins by enzyme-linked immunosorbent assay and neutralized the infectivity of HIV-1 LAI and ADA strains. T cells isolated from the mice responded to viral antigens by producing gamma interferon when analyzed by enzyme-linked immunospot assay. Importantly, exposure of the vaccinated animals to infectious HIV-1 demonstrated partial protection against infectious HIV-1 challenge. This was reflected by a reduction in HIV-1_ADA and by protection of the engrafted human CD4⁺T lymphocytes against HIV-1_LAI-induced cytotoxicity. These data demonstrate that transduction of DC by HSV amplicon vectors expressing HIV-1 gp120 induce virus-specific immune responses in hu-PBL-NOD/SCID mice. This mouse model may be a useful tool to evaluate human immune responses and protection against viral infection following vaccination.