## 1 Introduction  
Zika virus (ZIKV) and Yellow Fever virus (YFV) are both part of the flavivirus family, with enveloped, single-stranded, positive-sense RNA genomes. Both ZIKV and YFV are vectored by _Aedes_ mosquitoes. YFV and ZIKV originated in Africa and have been found to co-circulate within the same regions of Latin America [1]. ZIKV first appeared in the Western Hemisphere in 2015 [2; 3]. YFV, however, has been circulating in the Americas since the African slave trade era and is endemic in many tropical regions such as Brazil, Columbia, Venezuela, and Peru to name a few [4]. In the 1930s, a live attenuated vaccine for YFV, 17D, was developed and, in its almost 80 years of use, has proven to have a significant impact on controlling YFV outbreaks [4; 5]. Multiple countries have mass vaccination programs, and some countries, where YFV is endemic, have the YFV-17D vaccine included in the national recommended childhood immunization schedule. Particularly, Bolivia, Brazil, Columbia, Ecuador, and Venezuela all recommend the vaccine to children 9-12 months of age within the entire country, not just in known endemic regions [6]. Despite these recommendations, recent surveys showed that little more than half of the population in these regions are vaccinated for YFV [7]. With the ongoing vaccination campaigns in these areas, there are a spectrum of post-vaccination YFV antibodies, some of which might enhance infections by other flaviviruses. With many flaviviruses co-circulating in the same areas in Central and Southern America, there is the possibility of antigenic cross-reactivity, especially since some YFV-endemic areas have reported seroprevalence rates of ZIKV as high as 63% [4; 8]. Antigenic cross-reactivity and antibody-mediated enhancement frequently occur between flaviviruses. Cross-reactive Dengue virus (DENV) and West Nile virus antibodies have already been shown to enhance ZIKV pathogenesis [9; 10; 11]. However, only limited studies have been conducted on the potential cross-reactive nature of YFV antibodies. One study, using commercial ELISA detection kits for DENV and ZIKV, found there to be minimal cross-reactivity between YFV antibodies and DENV detection, and no cross-reactivity in ZIKV detection [12; 13]. While these studies were very informative, they did not represent the actual immunological landscape, as [PERSON] et al. [12] used post-vaccination serum from 9-month-old infants, who have an undeveloped immune system, and the CDC MAC-ELISA for ZIKV was validated using a sample size of fewer than 10 individuals, of an unknown exposure history [13]. Furthermore, South America, especially Brazil, has a high incidence of measles, which can affect immunological memory in recovered persons [14]. This, however, does not indicate possible in vivo interactions, as several reports indicate that flaviviral neutralization is complex and dependent upon many factors [15]. It has also been shown that antibodies that neutralize in vitro, such as in neutralization assays, often do not neutralize in vivo, suggesting that complex immunological interactions occur for neutralization [16; 17; 18]. In regions where ZIKV has a high prevalence, a large portion of the population also has YFV antibodies, not only from the childhood schedule of immunizations but also from ongoing vaccination campaigns that inoculate adults and provide boosters for pregnant women, HIV-infected persons, and other immunocompromised populations [19]. With a spectrum of YFV antibodies present in this population, it is important to understand any possible cross-reactivity, antibody-mediated enhancement, or antibody-mediated neutralization. Studies have reported that the vaccination of pregnant women with YFV occurs during vaccination campaigns [20; 21]. While several studies have shown that vaccination with YFV during pregnancy is safe, the development of protective immunity is reduced, indicating that there may be increased non-neutralizing, cross-reactive antibodies [19; 20; 21].