title: 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.
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 replication-defective, 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.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.forename: Kathlyn
authors.initials: K
authors.lastname: Santos
authors.forename: Vakara
authors.initials: V
authors.lastname: Meyer
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.forename: William J
authors.initials: WJ
authors.lastname: Bowers
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Larisa
authors.initials: L
authors.lastname: Poluektova
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004279:DNA, Viral; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000637:transplantation*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006378:Helper Viruses; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
chemical_list: D004279:DNA, Viral; D015699:HIV Envelope Protein gp120