Study On Protection Meachanism For Controlling SIV Infection By A Novel Vaccine Regimen In Rhesus Monkeys

The HIV/AIDS pandemic has been a serious challenge to human health and social stability. Up to now, about 40 million persons are living with HIV-1 infection, and more than 30 millions had already died from HIV-induced disease worldwide. Moreover,there are still an estimated 15,000 new HIV infections occurring every day. But so far, there are no a safe and effective AIDS vaccine to control the HIV epidemic yet. Because one of most popular routes for HIV infection is by sexual transmission, and meanwhile the intestinal mucosa are storing a large number of activated CD4+T lymphocytes, therefore, development of an effective vaccine to control HIV infection, especially preventing mucosal exposure, has been a urgent Scientific problems.After years of hard work of Laboratory collegues, we have developed a novel prime-boost regimen consisting of a MVTT (modified vaccinia Tiantan) vectored and rAd vectored SFV vaccine, which could elicite cellular immune responses with enhanced magnitude, sustainability, and poly-functionality. Most importantly, this strategy can prevent and control SIV challenge through mucosa surface, and it afforded a significant immune control of viral replication during both acute and chronic phases of infection and a slower rate of disease progression. However, the mechanism for this significant protection is still unclear. We attempt to elaborate the mechanism of this protective effect in this study.First, we find that this MVTT prime/rAd boost strategy can reduce the loss of CD4+T cells from the intestinal mucosal surface, which might enhance the protection. Second, We further detected the different cytokines expression by lunminex assay, and the SIV-specific IgG and IgA antibody titer. Third, Intestinals tissue and the gut associated lymphoid tissues were collected from these rhesus macaques, the possible immune mechanism of this protection was explored using HE staining, immunohistochemical staining, fluorescence quantitative PCR assays to detect the morphological pathology, viral copies, immunology and so on. Our data show that this mucosal immunization strategy may reduce the loss of intestinal lymphocyte, reduce the damage of the intestinal tract, and can curb the integrated SIV DNA copies, which may be associated with the protecion.These data suggested that our strategy induced effective mucosal immune responses, and played a protective effect in mucosal tissues. These data provide strong support for further study that the intestinal mucosa play an important role in controlling SIV infection, and laid a theoretical basis for future research and development of more effctive mucosal vaccine.