Development of a Zika Virus Vaccine
Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. Development of Zika virus vaccine is critical to prevent congenital zika syndrome in infants born to infected pregnant mothers. The measles vaccine has a long-standing history of safety, efficacy and durable responses. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2 protected mice from the non-lethal Zika Asian strain (PRVABC59), and from the lethal African strain (MR766) challenge. The MV-E2 vaccine was also efficacious when administered intramuscularly. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. Additionally, pre-existing Measles vaccine immunity dramatically affected the immunogenicity of both the MV-E2 and the MV-E0 vaccine, suggesting that our target population would be 6-month-old infants. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1), and we observed complete clearance of ZIKV from the female reproductive tract, and excellent fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract. The combination vaccine also induced durable plasma cell responses. These findings bring us closer to the advancement of a successful vaccine against Zika virus disease and have important implications in rethinking vaccine design strategies for the current Zika vaccines in clinical trials.
Kurup, Drishya, "Development of a Zika Virus Vaccine" (2020). ETD Collection for Thomas Jefferson University. AAI27958040.