EDIII-Fc induces protective immune responses against the Zika virus in mice and rhesus macaque

摘要

Zika virus can infect the fetus through the placental barrier, causing ZIKV congenital syndrome and even miscarriage, which can cause great harm to pregnant women and infants. Currently, there is no vaccine and drug available to combat the Zika virus. In this study, we designed a fusion protein named EDIII-Fc, including the EDIII region of Zika E protein and human IgG Fc fragment, and obtained 293T cells that stably secreted EDIII-Fc protein using the lentiviral expression system. Mice were immunized with the EDIII-Fc protein, and it was observed that viral replication was significantly inhibited in the immunized mice compared to non-immunized mice. In rhesus macaques, we found that EDIII-Fc effectively induce the secretion of neutralizing antibodies and T cell immunity. These experimental data provide valid data for further use of Zika virus E protein to prepare an effective, safe, affordable Zika vaccine. @@@ Zika virus (ZIKV) is a member of the Flavivirus genus. ZIKV could be transmitted through mosquito bites. In the population, ZIKV can be transmitted through mother-to-child transmission, sexual transmission, and blood transmission. Clinical symptoms of ZIKV infection in adults include rash, fever, arthralgia, and conjunctivitis, and neurological symptoms in those with severe infection, manifesting as Guillain-Barre syndrome (GBS). ZIKV can infect the fetus through the placental barrier, causing ZIKV congenital syndrome and even miscarriage. ZIKV causes fatal damage to the central nervous system of infants. Due to the lack of effective drugs, vaccination is the main strategy to against ZIKV. Conventional vaccines against the Zika virus have the potential to cause antibody-dependent enhancement (ADE). In this study, the authors designed a fusion protein named EDIII-Fc, including the EDIII region of Zika E protein and human IgG Fc fragment. EDIII protein has been shown to be incapable of causing ADE. Mice and rhesus monkeys were immunized with EDIII-Fc. EDIII-Fc could induce protective antibodies in mice and rhesus monkeys and protect mice against the challenge of ZIKV. These experimental data provide valid data for further use of ZIKV E protein to prepare an effective, safe, affordable Zika vaccine.

关键词