Antibodies protect the developing fetus from Zika virus infection

  When Zika virus infection is most severe, it can cause microcephaly or abnormal small heads in babies infected in utero. Today, researchers at Washington University School of Medicine and Vanderbilt University School of Medicine in St. Louis have confirmed that the application of human antibodies in pregnant mice can prevent fetal infection with Zika virus and damage to the placenta! The antibody can also protect adult mice from Zika virus disease.

  Michael Diamond is a doctor of pathology and medicine, Herbert S. Gasser's professor of medicine and the co-corresponding author of this study. He said: "This is the first antiviral drug that has been proven to be effective in protecting the fetus from Zika virus infection during pregnancy." "This also proves that Zika virus can be treated during pregnancy, and we A human antibody has been developed to treat this virus, at least it is effective in mice."

  This research was published in the November 7th issue of Nature as a fast-track online publication.

  Diamond and co-corresponding author James Crowe Jr (Ph.D. in Pathology, Vanderbilt University School of Medicine), and colleagues in the research team screened 29 anti-Zika virus antibodies from people who recovered from infection with Zika virus. They discovered an antibody named ZIKV-117, which can effectively neutralize five Zika virus strains in the laboratory, which represent the global diversity of the virus.

  In order to test whether the antibody can also protect live animals, the researchers applied it to pregnant mice one day before or one day after infection with Zika virus. In the above two experimental protocols, compared to pregnant mice that did not obtain the antibody, antibody treatment can significantly reduce the level of virus in pregnant mother mice and fetuses, and it is also effective in the placenta.

  Crowe said: "These naturally-occurring antibodies isolated from the human body represent the first level of medical intervention, which can cut off Zika virus infection and prevent fetal damage."

  The placenta of the mother mouse treated with antibody showed normal and healthy structure, while the placenta of the untreated mother mouse showed that the placenta structure was destroyed. The destruction of the placenta caused by human Zika virus infection can cause fetal growth retardation and may even cause fetal death.

  Indira Mysorekar is the co-author of the study, an associate professor in the Department of Obstetrics and Gynecology, Pathology and Immunology, and the director of the Center for Reproductive Sciences at the University of Washington School of Medicine. He pointed out: “We did not see any damage to fetal blood vessels, thinning of the placenta, or any growth restriction problems by the virus in the mouse fetuses treated with antibodies. Anti-Zika virus antibodies prevent the virus from passing through. The placenta, thereby protecting the fetus from damage."

  The antibody can also protect adult male mice against lethal doses of Zika virus infection, even five days after the initial infection. Zika virus is generally not lethal to humans, so scientists can use lethal doses of the virus to observe how antibodies work under the strongest infection conditions.

  Diamond, another professor of pathology, immunology, and molecular microbiology, said: “We tried to use the highly pathogenic Zika virus strain to refute our conclusions, but even in this case, antibodies can still affect mice. To protect."

  These findings indicate that antibodies can protect adults and fetuses from Zika virus infection. In addition, they believe that vaccines that obtain protective antibodies from women can also protect the fetus of women who are already pregnant or about to become pregnant. There is a vaccine that has been tested on humans, but it has not been tested on pregnant animals, so this new study strongly proves that vaccines that can produce protective antibodies in adults may also protect fetuses. .

  Zika virus vaccine may be the cheapest and easiest way to prevent Zika virus-related neonatal defects. However, there is still an extreme possibility that the Zika virus vaccine can make the symptoms of patients with advanced Zika virus infection worse. This phenomenon also occurs in the course of dengue virus infection, which is a virus closely related to Zika virus. Those who already have antibodies to a certain dengue virus strain will be more severely ill when infected with the second dengue virus strain than those who do not have such antibodies. This phenomenon is called "antibody-dependent enhancement" and has been observed in petri dishes containing Zika virus, but it has never been found in live animals or surveyed populations in Zika virus endemic areas.

  Despite this, researchers need to test whether they can modify the antibody to prevent the antibody from participating in order to avoid the increase in antibody dependence during Zika virus infection. They said: The modified antibody and the original antibody have the same effect on the protection of the placenta and fetus.

  Before the human vaccine is available, in order to prevent the mother from spreading the virus to the fetus, pregnant women can be injected with antibodies to protect the fetus. In this case, a woman living in a Zika virus-endemic area can get the antibody during her pregnancy, regardless of whether she is diagnosed with Zika virus or not, she can get the antibody when she first learns of her pregnancy. antibody. In addition, pregnant women or partners with acute infections can be treated with antibodies.

  Crowe is continuing to develop antibodies as a potential therapeutic method, and is stepping up production to lay the foundation for the application of antibodies to human research. During this period, Diamond is working on studying whether antibodies can be used to clear persistent viral infections. At the same time, they are working with other researchers to understand more clearly how ZIKV-117 binds to the virus and prevents infection.

  Diamond said: "Zika virus can persist in certain parts of the body, such as the eyes and testes, where it can cause long-term damage, at least in mice. This antibody can stop the disease. Now we want to Know whether it can clear persistent infections in those parts of the body."