An Adjuvanted Herpes Simplex Virus Type 2 (HSV-2) Subunit Vaccine Elicits a T Cell Response In Mice and Is an Effective Therapeutic Vaccine In Guinea Pigs.

Genocea Biosciences, Inc., Cambridge, MA 02140.
Journal of Virology (Impact Factor: 4.65). 01/2013; DOI: 10.1128/JVI.02745-12
Source: PubMed

ABSTRACT Immunotherapeutic herpes simplex virus type 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 (gD2rTMR(340-363)) and a truncated form of infected cell polypeptide 4 (ICP4(383-766)), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells were induced in immunized mice, characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that could be recalled at least 44 days after the last immunization. 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 PBS control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, it was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2- 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.

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