A Zika virus vaccine is designed to prevent the symptoms and complications of Zika virus infection in humans. As Zika virus infection of pregnant women may result in congenital defects in the newborn, the vaccine will attempt to protect against congenital Zika syndrome during the current or any future outbreak. As of April 2019, no vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials. The goal of a Zika virus vaccine is to elicit protective antibodies against the Zika virus to prevent infection and severe disease. The challenges in developing a safe and effective vaccine include limiting side effects such as Guillain-Barré syndrome, a potential consequence of Zika virus infection. Additionally, as dengue virus is closely related to Zika virus, the vaccine needs to minimize the possibility of antibody-dependent enhancement of dengue virus infection.

As of March 31, 2017 a DNA vaccine has been approved for Phase 2 clinical trials in humans. The vaccine consists of a DNA plasmid encoding the E and PrM proteins which make up the outer protein coat of the Zika virus virion. Based on a previous platform used to develop a West Nile virus vaccine, the DNA vaccine is designed to assemble protein particles that mimic Zika virus and trigger the body's immune response. A live attenuated vaccine, in which the virus is genetically altered as to not cause disease in humans, is undergoing phase 1 clinical trials. This vaccine is based on the dengue vaccine Dengvaxia, which has been approved for use in humans. A modified mRNA vaccine developed in collaboration with Moderna Therapeutics containing the E and PrM proteins is undergoing concurrent phase 1 and 2 clinical trials. Multiple vaccines are also being developed using safe, non-pathogenic, viruses as vectors for immunogenic Zika virus proteins. One phase 1 trial is using the Measles virus as a vector and was completed in April 2018. Another vaccine platform makes use of Adenovirus as a vector and phase 1 studies will be complete in 2019. Adenoviruses have been previously used as a vaccine platform for HIV and elicit a strong immune response.