Abstract: Herpes simplex virus type 2 (HSV-2) is a one of the most prevalent worldwide sexually transmitted infection. HSV-2 causes recurrent genital ulcers, neonatal herpes, and also, increases the risk for HIV acquisition. Many HSV-2 vaccines have been tested in humans, but were not consistently effective. In the present work we tried to produce a model vaccine for HSV-2 formulated in different formulae as an attempt for development of an effective prophylactic and therapeutic HSV-2 vaccine. Beta propiolactone (BPL) as virus inactivant was compared with the conven¬tional formalin. Also, calcium phosphate nano-particles (CPN) as a vaccine adjuvant was compared with current used aluminum phosphate gel (alum) micro-particles. Stability of adjuvanted and non adjuvanted vaccine models was monitored at different thermal conditions. Subcutaneous route was conducted in balb-c mice to determine the immune response of vaccine formulations. Data revealed that Al-BPL-HSV-2 vaccine showed the highest and longer durative immune response compared with other vaccine candidates. Different formulations of the test vaccine showed the same pattern of stability at different thermal conditions (4oC and 37oC and 45oC). Also, Al-BPL-HSV-2 vaccine formulation could efficiently develop antibody level that could neutralize the challenge dose of HSV-2 and no viral infection could be detected in the vaginal tissues using direct immune-fluorescent assay.