动物实验 z-bo 2020-08-27 435

　　If the Zika virus infection is the most severe, it may cause microcephaly or unusually small heads in babies with uterine infections. Today, researchers at Washington University School of Medicine and Vanderbilt University School of Medicine confirmed that applying human antibodies to pregnant mice can prevent fetal infection and Zika virus damage to the placenta. The antibody can also protect adult mice from Zika virus disease.

　　Michael Diamond is a professor of medicine, a doctor of pathology and medicine at Herbert S. Gasser, and a co-author of the study. "This is the first antiviral drug proven to be effective in protecting fetuses from Zika virus infection during pregnancy." "This also proves that Zika virus can be treated during pregnancy. At least it has been developed in mice. Human antibodies to treat this virus."

　　Diamond and its corresponding author James CroweJr (Ph.D. in Pathology, Vanderbilt University School of Medicine) and colleagues in their research team screened 29 anti-Zika virus antibodies from people who recovered from Zika virus infection. They discovered an antibody called ZIKV-117. It can effectively neutralize five Zika virus strains in the laboratory, representing the global diversity of the virus. To test whether the antibody can protect living animals, the researchers applied the antibody to pregnant mice 1 or 1 day before Zika virus infection. In the above two experimental schemes, compared with pregnant mice without antibodies, antibody treatment can significantly reduce the virus levels of pregnant mice and fetuses, and it is also effective on the placenta. Yes.

　　Crowe: "These naturally occurring antibodies isolated from the human body represent the first stage of medical intervention that can prevent Zika virus infection and prevent fetal harm."

　　The placenta of the treated mother mouse was normal, and the placenta of the untreated mother mouse showed that the placenta structure was damaged. The destruction of the placenta caused by human Zika virus infection can lead to fetal growth retardation and even fetal death.

　　Indira Mysorekar is a co-author of this study, an associate professor of obstetrics and gynecology, pathology, and immunology, and the director of the Center for Reproductive Sciences at the University of Washington School of Medicine. "In antibody-treated mouse fetuses, we have not found fetal blood vessel damage, thinning of the placenta or restricted viral growth. Anti-Zika virus antibodies prevent the virus from using it to protect the fetus by destroying the placenta."

　　"This antibody can protect adult male mice from a lethal dose of Zika virus infection, even five days after the first infection. Zika virus usually has no lethal effects on humans, so scientists can use lethal doses of the virus to observe the effects of antibodies under the strongest infection conditions. Diamond, another professor of pathology, immunology, and molecular microbiology, said: “We tried to conclude that the highly pathogenic Zika virus strain was used, but these antibodies again showed that these antibodies can protect adults and fetuses from Zika. Viral infection.” In addition, we believe that vaccines that obtain protective antibodies from women can also protect the fetuses of women who are or will be pregnant. These fetuses have been tested in humans but have not been tested in pregnant animals. With this vaccine, this new study strongly proves that a vaccine that can produce protective antibodies in adults can also protect fetuses. The Zikavirus vaccine can prevent newborn defects associated with the Zika virus. This is the cheapest and simplest method, but the Zika virus vaccine is still likely to aggravate the symptoms of patients with advanced Zika virus infection, which is a virus closely related to dengue fever and Zika virus. It can also occur during the course of infection: people who have been infected with a specific strain of dengue fever are more severely infected with the second strain of dengue virus than those without. This phenomenon is called "antibody-dependent enhancement" and has been observed in petri dishes containing Zika virus, but not in living animals or people surveyed in areas where Zika virus is endemic. Nevertheless, researchers still need to test whether antibodies can be modified to avoid the enhancement of antibody-dependent Zika virus infection. They said: The modified antibody and the original antibody have the same effect on the protection of the placenta and fetus. To prevent the mother from spreading the virus to the fetus before getting the human vaccine, the pregnant woman can be injected with antibodies to protect the fetus. In this case, women living in Zika virus endemic areas can obtain antibodies during pregnancy, regardless of whether they are diagnosed with Zika virus. She can get antibodies when she first knows she is pregnant. antibody. In addition, pregnant women and partners with acute infections can be treated with antibodies. Crowe continued to develop antibodies as potential therapies and increased production, laying the foundation for the application of antibodies to human research. During this time, Diamond is studying whether antibodies can be used to eliminate persistent viral infections. At the same time, they are collaborating with other researchers to better understand how ZIKV-117 binds to the virus and prevents infection.

　　Diamond: "Zika virus persists in certain parts of the human body (such as the eyes and testes) and causes long-term damage at least in mice. This antibody can stop this disease. I wonder if I can eliminate these parts Persistent infection."