Th1-associated immune responses to beta-galactosidase expressed by a replication-defective herpes simplex virus
| Autor: | J O Brubaker, C M Thompson, L A Morrison, D M Knipe, G R Siber, R W Finberg |
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| Rok vydání: | 1996 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 157:1598-1604 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.157.4.1598 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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