Th1-associated immune responses to beta-galactosidase expressed by a replication-defective herpes simplex virus.
The immunogenic properties of a replication-defective herpes simplex virus HD-2, containing the Escherichia coli lacZ gene under control of the HSV ICP8 early gene promoter were studied in BALB/c mice. Experiments were designed to determine if the HD-2 virus preferentially stimulated either Th1- or Th2-associated immune responses to beta-galactosidase (beta gal). Sera from mice immunized i.p. or s.c. with virus HD-2, beta gal on aluminum phosphate adjuvant, or a control ICP8 deletion mutant, d301, were assayed for total and Ag-specific IgG1 and IgG2a Abs, beta gal-driven lymphocyte proliferation, and in vitro production of the cytokines IFN-gamma, IL-4, and IL-2. Viruses HD-2 and d301 preferentially stimulated the production of total serum IgG2a following two immunizations i.p. or a single immunization s.c., while only HD-2 virus stimulated in vivo production of beta gal-specific IgG2a serum Abs. In contrast, beta gal adsorbed on AIPO4 preferentially stimulated production of Ag-specific IgG1 serum Abs. The HD-2 virus also induced a potent cellular proliferative response to beta gal, which was still pronounced 5 wk after primary immunization. Cultured lymphocytes from HD-2-immunized mice produced IFN-gamma after 5 days in culture with soluble beta gal in an Ag- and dose-dependent fashion. These results demonstrate that replication-defective mutants of HSV can be used as vectors for eliciting Th1-associated immune responses to a heterologous Ag expressed from the viral genome.
Brubaker
J O
JO
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Thompson
C M
CM
Morrison
L A
LA
Knipe
D M
DM
Siber
G R
GR
Finberg
R W
RW
D000818:Animals; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics* / Q000502:physiology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D018139:Simplexvirus / Q000235:genetics* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D007371:Interferon-gamma; D001616:beta-Galactosidase