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

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.