AG-707

AG-707 is a polyvalent off the shelf therapeutic heat shock protein based vaccine for treatment of genital herpes which has completed Phase 1 clinical testing. AG-707 consists of recombinant human heat shock protein-70 complexed with 32 distinct 35-mer synthetic peptides from the HSV-2 proteome. The completed trial 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 show that AG-707 administered with QS21 adjuvant was associated with a significant induction of both CD4+ in 7/7 subjects (100%) and CD8+ in 5/8 subjects (63%) cellular immune response.

This is the first instance of a polyvalent herpes vaccine eliciting both CD4 and CD8 cellular immunity in human subjects. This finding is consistent with the known mechanism of action of AG-707. In addition, AG-707 administration (with and without QS-21) was feasible and well tolerated.

There is a strong scientific rationale for developing a herpes vaccine that is focused on T cell generation, like AG-707. 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, AG-707 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 AG-707 is intended to allow for more accurate immune targeting and surveillance, reducing the likelihood of immune escape. Further, the diversity of antigens in AG-707 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.