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An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in Guinea pigs.
- Source :
-
Journal of virology [J Virol] 2013 Apr; Vol. 87 (7), pp. 3930-42. Date of Electronic Publication: 2013 Jan 30. - Publication Year :
- 2013
-
Abstract
- Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.
- Subjects :
- Analysis of Variance
Animals
Baculoviridae
Blotting, Western
Chlorocebus aethiops
Cloning, Molecular
DNA Primers genetics
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
Guinea Pigs
Herpes Genitalis therapy
Mice
Neutralization Tests
Vero Cells
Viral Envelope Proteins immunology
Viral Vaccines pharmacology
Virus Shedding immunology
Adjuvants, Immunologic pharmacology
Herpes Genitalis immunology
Herpesvirus 2, Human immunology
Immunotherapy methods
T-Lymphocytes immunology
Viral Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 87
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 23365421
- Full Text :
- https://doi.org/10.1128/JVI.02745-12