Studies On GD And UL25 Immunogens Of Herpes Simplex Virus Type 2 Vaccine

Herpes simplex virus（HSV-2） is a common neurological autophagy virus, HSV-2 infection is mainly produced by sexual transmission of genital tract secretions, increase the incidence of cervical cancer, penile cancer, prostate cancer, due to infection with HIV-1 is easy to increase the risk of HIV/AIDS infection 3-4 times. HSV-2 the special biological characteristics including latent and relapse, and it can escape the host’s immune response, latent central nervous system of dorsal root ganglion, establish lifelong latent, break out repeatedly, cannot be cured. As the most easy to recurrent genital herpes, genital infection caused by HSV-2 there are three main clinical stages: primary and recurrent and subclinical. There are currently no effective drug in the treatment of recurrent and subclinical genital herpes virus infection, so the vaccine research for the prevention of HSV-2 primary infection, control the latent HSV-2 lead to recurrent infection and detoxification and subclinical infection of HSV-2 spread has very important significance. Despite the current HSV-2vaccine has not been approved, but most of the clinical trial results show that HSV-2 envelope glycoprotein gD is the most key proteins mediated virus into the host cell, can induce the body to produce high levels of neutralizing antibodies and strong cellular immune response, and get better at the animal level protection after tapping the poison.Many clinical experimental results also showed that cellular immune response in the inhibition of virus latent, removal and control of latent HSV-2 lead to the important role of recurrent infection, including UL25 capsid protein was proved to be able to induce high levels of T cell immune response, UL25 contains rich CD8 + T cell epitope. Adenovirus vector can efficiently transfer and expressed genes, with adenovirus as a carrier of the vaccine is effective leads to higher levels of neutralizing antibody specificity, adenovirus type 5（Ad 5） is currently the most commonly used packaging adenovirus carrier.This paper establishes（1） the model of Balb/c on toxic dose of groping, determines the Balb/c deadly poison attack dose for 1×10⁵ pfu/mouse, and calculate the median lethal dose of 1.2×10⁴ pfu/mouse.（2） build and packaging as the rAd-Δ UL25 recombinant adenovirus vector vaccine, with the rAd-gD2, rAd-gD2ΔUL25, together with the traditional fire extinguishing FI-HSV-2 and drug Acyclovir contrast, use of prophylactic vaccine Balb/C against poison animal models, to compare the immunogenicity and protection after tapping the poison. After 10 times the results show that the LD₅0 poison attack, rAd-gD2, rAd-gD2ΔUL25 can induced high levels of gD2, neutralizing antibody level and specific binding of interferon- gamma levels; As rAd-ΔUL25, rAd-gD2 can produce UL25 specificity for LP2 interferon- gamma level; In terms of attack after poison protection, as compared with other groups of rAd-gD2ΔUL25 presents the highest survival rate and the fastest virus removal rate.（3） using the guinea pig therapeutic vaccines against poison animal model, evaluated as rAd-ΔUL25, rAd-gD2, rAd-gD2ΔUL25, FI-HSV-2, the traditional fire extinguishing vaccine and drug Acyclovir against the attack of poison protection and HSV-2 after the latent virus removal and viruses. As the result shows: the rAd-gD2ΔUL25 in guinea pig models still showed the highest survival rate and the fastest virus removal rate; rAd-gD2 show slightly higher than FI-HSV-2, as the rAd-ΔUL25 presents the negative result, illustrates the individual immune ΔUL25 to induced ΔUL25 specificity of T cell immune response but no obvious poisonous attack protection, after separate immune epitope gD2 gD specificity can be induced to produce good immunogenicity and protection, the effect is lower than as rAd-gD2ΔUL25. As and when the gD2 and ΔUL25 two tables and a coupling on the immune, as rAd-gD2ΔUL25 showed the strongest immunogenicity and the best protection.