Recombinant vesicular stomatitis virus vectors expressing herpes simplex virus type 2 gD elicit robust CD4+ Th1 immune responses and are protective in mouse and guinea pig models of vaginal challenge
| Autor: | David K. C. Cooper, Diane Pawlyk, Min Guo, Farooq Nasar, Margaret Lee, Jacek Kowalski, David K. Clarke, R. Michael Hendry, Priscilla Calderon, Stephen A. Udem, Susan E. Witko, John H. Eldridge, Joanne DeStefano, Seema S Gangolli, Kevin J. Wright, Narender K. Kalyan, Aaron S. Abramovitz, Donna Tummolo, Robert J. Natuk |
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| Rok vydání: | 2006 |
| Předmět: |
Herpesvirus 2
Human Immunology Genetic Vectors Guinea Pigs Recombinant virus medicine.disease_cause Microbiology Virus Immunoglobulin G Vesicular stomatitis Indiana virus Mice Immune system Viral Envelope Proteins Virology Vaccines and Antiviral Agents medicine Animals Mononegavirales Glycoproteins biology Immunogenicity Herpes Simplex Virus Vaccines Th1 Cells biology.organism_classification Herpes simplex virus Vesicular stomatitis virus Insect Science Antibody Formation Models Animal Vagina biology.protein Female |
| Zdroj: | Journal of Virology |
| ISSN: | 0022-538X |
| Popis: | Recombinant vesicular stomatitis virus (rVSV) vectors offer an attractive approach for the induction of robust cellular and humoral immune responses directed against human pathogen target antigens. We evaluated rVSV vectors expressing full-length glycoprotein D (gD) from herpes simplex virus type 2 (HSV-2) in mice and guinea pigs for immunogenicity and protective efficacy against genital challenge with wild-type HSV-2. Robust Th1-polarized anti-gD immune responses were demonstrated in the murine model as measured by induction of gD-specific cytotoxic T lymphocytes and increased gamma interferon expression. The isotype makeup of the serum anti-gD immunoglobulin G (IgG) response was consistent with the presence of a Th1-CD4+anti-gD response, characterized by a high IgG2a/IgG1 IgG subclass ratio. Functional anti-HSV-2 neutralizing serum antibody responses were readily demonstrated in both guinea pigs and mice that had been immunized with rVSV-gD vaccines. Furthermore, guinea pigs and mice were prophylactically protected from genital challenge with high doses of wild-type HSV-2. In addition, guinea pigs were highly protected against the establishment of latent infection as evidenced by low or absent HSV-2 genome copies in dorsal root ganglia after virus challenge. In summary, rVSV-gD vectors were successfully used to elicit potent anti-gD Th1-like cellular and humoral immune responses that were protective against HSV-2 disease in guinea pigs and mice. |
| Databáze: | OpenAIRE |
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