Yellow Fever Vaccine Protects Resistant and Susceptible Mice Against Zika Virus Infection

Abstract

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. The development of an effective vaccine against Zika virus is a public health priority, encouraging the preclinical and clinical studies of different vaccine strategies. Here, we describe the protective effect of an already licensed attenuated yellow fever vaccine (17DD) on type-I interferon receptor knockout mice (A129) and immunocompetent (BALB/c) mice infected with ZIKV. Yellow fever virus vaccination results in robust protection against ZIKV, with decreased mortality in the A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in the BALB/c mice. Despite the limitation of yellow fever (17DD) vaccine to elicit antibody production and neutralizing activity against ZIKV, we found that YF immunization prevented the development of neurological impairment induced by intracerebral virus inoculation in adult. Although we used two vaccine doses in our protocol, a single dose was protective, reducing the cerebral viral load. Different Zika virus vaccine models have been tested; however, our work shows that an efficient and certified vaccine, available for use for several decades, effectively protects mice against Zika virus infection. These findings open the possibility for using an available and inexpensive vaccine to a large-scale immunization in the event of a Zika virus outbreak.

Does the Presence or a High Titer of Yellow Fever Virus Antibodies Interfere with Pregnancy Outcomes in Women with Zika Virus Infection?

“…Taken together, these studies suggest that the yellow fever vaccine may be important in the prophylaxis of ZIKV infections and their outcomes [23]. If the YFV vaccine really protects against ZIKV infection and its outcomes, there is a vaccination model that is safe, fast, and cheap, and whose safety is already well known [21,23]. In the present study, we ascertained the presence and titers of antibodies and outcomes in women who had a ZIKV infection during pregnancy and were followed up at a reference hospital for infectious diseases in the Brazilian Amazon, a region with massive immunization against YFV.…”

“…In type I interferon receptor knockout mice (A129) and BALB/c and SV-129 immunocompetent mice (A129 background), vaccination against YFV provided protection against ZIKV, reduced mortality and cerebral viral load in all mice, and prevented blood loss and loss of weight in BALB/c mice [23]. An in vitro assay showed that ZIKV was capable of infecting BeWo cell lines (derived from human placenta and mimicking the structure and function of the syncytiotrophoblast layer) and HU-VEC (umbilical vein cells), and YFV antibodies presented an impact on ZIKV, depending on the type of cell line.…”

“…One study hypothesized that children of pregnant women in regions with high YFV vaccination coverage have a lower risk of microcephaly; however, more appropriate study methodologies should be used [24]. Taken together, these studies suggest that the yellow fever vaccine may be important in the prophylaxis of ZIKV infections and their outcomes [23]. If the YFV vaccine really protects against ZIKV infection and its outcomes, there is a vaccination model that is safe, fast, and cheap, and whose safety is already well known [21,23].…”

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

“…As regards auditory assessment, only five children underwent the appropriate examination and one presented with alterations in the left ear. In children with microcephaly, the prevalence of hearing loss was 6.6% 23 . No child had a more specialized ophthalmological evaluation performed, such as fundoscopy, which prevents us from commenting on important limitations in vision.…”