Pre-Clinical Pregnancy Models for Evaluating Zika Vaccines

Zika virus (ZIKV) infection during pregnancy can result in a variety of developmental abnormalities in the fetus, referred to as Congenital Zika Syndrome (CZS). The effects of CZS can range from the loss of the viable fetus to a variety of neurological defects in full-term infants, including microcephaly. The clinical importance of ZIKV-induced CZS has driven an intense effort to develop effective vaccines. Consequently, there are approximately 45 different ZIKV vaccine candidates at various stages of development with several undergoing phase I and II clinical trials. These vaccine candidates have been shown to effectively prevent infection in adult animal models, however, there has been less extensive testing for their ability to block vertical transmission to the fetus during pregnancy or prevent the development of CZS. In addition, it is becoming increasingly difficult to test vaccines in the field as the intensity of the ZIKV epidemic has declined precipitously, making clinical endpoint studies difficult. These ethical and practical challenges in determining efficacy of ZIKV vaccine candidates in preventing CZS have led to increased emphasis on pre-clinical testing in animal pregnancy models. Here we review the current status of pre-clinical pregnancy models for testing the ability of ZIKV vaccines to prevent CZS.