The patient is waiting

Using an entirely new approach, clinicians at UW Seattle have generated unprecedented results with our HerpV vaccine candidate, which contains QS-21 Stimulon® adjuvant. Such breakthroughs are why we seek the right partners to speed promising new therapies to the clinic.

Agenus plans to advance HerpV into a Phase 2 study in 2012 that will measure the effect of vaccination on viral shedding in individuals infected with HSV-2. Experts in HSV-2 clinical research believe that a reduction in viral shedding could translate into clinical benefit.

Introduction

HerpV ('hərp•vē) is a polyvalent off-the-shelf therapeutic heat shock protein-based vaccine for treatment of genital herpes that has completed Phase 1 clinical testing. HerpV consists of recombinant human heat shock protein-70 complexed with multiple, distinct antigens from the HSV-2 proteome.

Progress

The Phase 1 trial completed with HerpV was a randomized, blinded study designed to determine vaccine safety and immunogenicity with particular focus on induction of cellular immune response.

The results of the study, published in Vaccine, show that HerpV administered with QS21 adjuvant was associated with a significant induction of both CD4+ in 7/7 subjects (100%) and CD8+ in 6/8 subjects (75%) cellular immune response.

This is the first instance of a polyvalent herpes vaccine candidate eliciting both CD4 and CD8 cellular immunity in human subjects. This finding is consistent with the known mechanism of action of HerpV. In addition, HerpV administration (with and without QS-21) was feasible and well tolerated.

Scientific Rationale

There is a strong scientific rationale for developing a herpes vaccine that is focused on T cell generation, like HerpV. Evidence has accumulated that CD8+ and CD4+ T cells localize to herpes skin lesions in humans and persist for many weeks after lesion healing; also, persistence of HSV-specific CD8+ T cells in neurons is associated with maintenance of viral latency. [click here for references] Further, it has been observed that robust CD4+ and CD8+ T cell activity against HSV-2 antigens can be detected in individuals who have clearly been exposed to HSV-2, yet remain HSV-2 seronegative and asymptomatic.[click here for reference]

Despite this evidence, many vaccine approaches to HSV-2 have focused on induction of antibody responses. Further, such efforts have included only a small number of HSV-2 antigens. Attempts to induce broader immune response (antibody and cellular) using attenuated or replication incompetent viruses have not been successful and carry potential safety or manufacturing concerns.

In contrast, HerpV is a highly multivalent synthetic vaccine that has been shown to induce CD4+ and CD8+ T cell responses. The broad spectrum of herpes antigens in HerpV is intended to allow for more accurate immune targeting and surveillance, reducing the likelihood of immune escape. Further, the diversity of antigens in HerpV increases the chance of providing protection for a wide segment of the patient population.

Besides herpes, HSPs can be used to generate multivalent vaccines against a wide range of infectious agents.