The Immune Effect Of HSV-2 GD Subunit Vaccine With BLP Adjuvant

Genital herpes is caused by herpes simplex virus type 2.There are more than 500 million people infected with HSV-2 virus all over the world.Once infected with HSV-2 virus,the virus will establish longlife latency and recurrence in sensory neuron of the host.It will cause serious physical trauma and psychological pressure to the infected patients.And the only way to treat genital herpes is antiviral drugs,such as acyclovir,but the antiviral drugs just could reduce the recurrence rate and severity of the diseased.They can't prevent viral transmission or eliminate the latency of HSV-2.Therefore,it is very necessary to develop a safe and effective vaccine against HSV-2.Current HSV-2 vaccine studies failed in focusing on inducing the neutralizing antibodies while ignoring the importance of cellular immune responses.Therefore,it is very important to keep balance cellular immune responses with humoral immune to ensure the effectivity of HSV-2 vaccines in the future.HSV-2 contains a protein on its surface known as glycoprotein D which it needs to enter host cells.The gD2-receptor(HVEM)interaction is suggested as a key factor for successful virus entry.Vaccines that contain glycoprotein D trigger the production of antibodies against HSV-2 gD2 could block the binding of gD2 with HVEM and prevent infection of HSV-2.Furthermore,gD2 is a major target for antibody epitopes and T cell epitopes that can induce relatively high neutralizing antibody and T cell immune response.We choose gD2 for the target of subunit vaccine.However,the immunogenicity of subunit vaccines is too low,we have to use the immunological adjuvant used together.Bacteria-like particles(BLP)is a novel mucosal adjuvant.BLP may be derived from inactivated Lactococcus lactis,the bacterium is safe and widely used in beverages and dairy products such as cheese and yogurt.BLP executes the adjuvant function by activating the innate immune system,then activation of specific immune response can eventually induce long-lasting protective immune response to protect the body against pathogen infection.Meanwhile,BLP not only can nasal immunization,but also can choose routes of immunization by intramuscular injection,which is better than the aluminum adjuvant after injection by inducing immune humoral immune response.Using genetic engineering technique to fusion express HSV-2 gD protein and protein connector(protan),then connect gD2 surface to the BLP for immunization experiment.This paper fusion express gD2-protan protein,and anchor on the surface of BLP,then immunize Balb/c mice by two different ways:intranasal and intramuscular.Assessing the vaccine by detecting vaccine-induced neutralizing antibodies and the ability to cause cellular immune response,protection in mice after challenge,the scavenging ability of HSV-2 in reproductive tract of mice.Also,verify that the safety and feasibility of BLP as a novel vaccine adjuvant.The results show that:the vaccine can induce high levels of neutralizing antibodies and can induce cellular immunity slightly.The vaccine can protect mice excellently after challenge,inhibit the replication of HSV-2 in reproductive tract.The novel vaccine adjuvant BLP can significantly enhance specific antibody titers and the antibody neutralizing capacity,increase the secretion of IFN-y and IL-2,and enhance cellular immune response.The vaccine with BLP can be better in increasing a higher survival,reducing the viral load in mouse reproductive tract after challenge.