Vaccines against varicella zoster virus gene 63 product

#The present invention relates to compositions for the treatment or prevention of Zoster of individuals infected with Varicella Zoster virus (VZV), and to the prevention and treatment of Varicella infections. The compositions of the invention comprise the protein encoded by VZV gene 63 or an immunologically active derivative thereof. The invention further relates to compositions containing DNA or RNA corresponding to VZV gene 63.

#Varicella Virus is a human alpha herpes virus which causes two human diseases: on primary infection VZV causes childhood chicken pox (Varicella) thereafter the virus becomes latent and frequently reactivates (often decades later) to produce shingles (Zoster). During chicken pox, the virus penetrates the peripheral nervous system where it remains latent until reactivates as the painful Zoster form. Whilst the virus is latent the expression of most viral genes are repressed. It is believed that cell mediated immunity plays a crucial role in the control of latency, since reactivation as Zoster (or shingles) is frequent in the elderly or in immunocompromised individuals.

#VZV infection is characterized by minimal presence of free virus. During latency and reactivation virus is mainly intracellular. Accordingly, recurrent disease is not prevented even by high levels of neutralizing antibodies and virus control depends on cell mediated immunity. In order to obtain protection by vaccination, it is therefore desirable to induce not just an antibody response, but also a CTL response. An effective vaccine should prime CTL capable of acting as early as possible as soon as signs of reactivation of latent virus appear.

#FIG. 1. Stimulation Index (S.I.) obtained after stimulation with whole VZ antigens or with IE63. T lymphocyte stimulation was determined by stimulation of PBMC (Peripheral Blood Mononucles cytes) isolated by ficollhypaque centrifugation. The stimulation index (SI) was calculated as the ratio of CPM in protein stimulated wells versus control wells, and was considered as positive if greater than 2.

#FIG. 2. PBMC from 19 healthy adults were assayed for T cell proliferation in response to stimulation with either VZV antigens or GST-IE63 purified protein. When S.I. after VZV stimulation were plotted and compared to the S.I. with GST-IE63, the two non immune patients appeared clearly negative (S.I. less than 2.0) with both antigen preparations.

#FIG. 3. When T cell populations recovered by T-Lymphokwik were used, the lysis of targets expressing VZV proteins was significantly higher than the one observed for the uninfected or control targets as demonstrated for one assay.

#The two adjuvant formulations are made each comprising the following oil in water emulsion component.

#SB 62:5% squalene 5% tocopherol 2.0% tween 80; the particle size was 180 nm

#1(a) Preparation of Emulsion SB62 (2 Fold Concentrate)