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

Abstract

Zika virus (ZIKV) and yellow fever virus (YFV) originated in Africa and expanded to the Americas, where both are co-circulated. It is hypothesized that in areas of high circulation and vaccination coverage against YFV, children of pregnant women have a lower risk of microcephaly. We evaluated the presence and titers of antibodies and outcomes in women who had ZIKV infection during pregnancy. Pregnancy outcomes were classified as severe, moderate, and without any important outcome. An outcome was defined as severe if miscarriage, stillbirth, or microcephaly occurred, and moderate if low birth weight and/or preterm delivery occurred. If none of these events were identified, the pregnancy was defined as having no adverse effects. A sample of 172 pregnant women with an acute ZIKV infection confirmed during pregnancy were collected throughout 2016. About 89% (150 of 169) of them presented immunity against YFV, including 100% (09 of 09) of those who had severe outcomes, 84% (16 of 19) of those who had moderate outcomes, and 89% (125 of 141) of those who had non-outcomes. There was no difference between groups regarding the presence of anti-YFV antibodies (p = 0.65) and YFV titers (p = 0.6). We were unable to demonstrate a protective association between the presence or titers of YFV antibodies and protection against serious adverse outcomes from exposure to ZIKV in utero.

Mechanisms of Flavivirus Cross-Protection against Yellow Fever in a Mouse Model

“…Experimental studies to investigate a pathogen often focus only on that specific pathogen, discounting the influence of immunity from related pathogens in endemic regions or in an outbreak setting. In the context of flaviviruses, numerous human cohort studies focus on understanding the immune response and the role of pre-existing immunity from primary infection in the course of disease during secondary infection, a phenomenon that has particularly been important in DENV infections due to its association with antibody-dependent enhancement (ADE) [ 32 , 33 , 34 ]. Several studies seeking to determine the role of DENV immunity in ZIKV infection and vice versa have been reported since the massive ZIKV outbreak starting in 2015 in South America, a region that is hyper-endemic for DENV [ 34 , 35 , 36 , 37 ].…”