Identification of novel virus-specific antigens by CD4⁺ and CD8⁺ T cells from asymptomatic HSV-2 seropositive and seronegative donors.

Reactivation of latent herpes simplex virus 2 (HSV-2) infections can be characterized by episodic recurrent genital lesions and/or viral shedding. We hypothesize that infected (HSV-2(pos)) asymptomatic individuals have acquired T cell responses to specific HSV-2 antigen(s) that may be an important factor in controlling their recurrent disease symptoms. Our proteomic screening technology, ATLAS, was used to characterize the antigenic repertoire of T cell responses in infected (HSV-2(pos)) and virus-exposed seronegative (HSV-2(neg)) subjects. T cell responses, determined by IFN-γ secretion, were generated to gL, UL2, UL11, UL21, ICP4, ICP0, ICP47 and UL40 with greater magnitude and/or frequency among cohorts of exposed HSV-2(neg) or asymptomatic HSV-2(pos) individuals, compared to symptomatic recurrent HSV-2(pos) subjects. T cell antigens recognized preferentially among individuals who are resistant to infection or who are infected and have mild or no clinical disease may provide new targets for the design of vaccines aimed at treating and/or preventing HSV-2 infection.

An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in Guinea pigs.

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.