Clinical and Immunological Insights on Severe, Adverse Neurotropic and Viscerotropic Disease following 17D Yellow Fever Vaccination

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Abstract
Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-γR in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3 + CD16 +/− CD56 +/− /CD3 + ratio), activated T cells (CD4 + and CD8 + cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-γ + ], tumor necrosis factor alpha positive [TNF-α + ], and IL-4 positive [IL-4 + ]), CD8 + T cells (IL-4 + and IL-5 + ), and B lymphocytes (TNF-α + , IL-4 + , and IL-10 + ). The analysis of CD4 + T cells revealed a complex profile that consisted of an increased frequency of IL-12 + and IFN-γ + cells and a decreased percentage of TNF-α + , IL-4 + , and IL-5 + cells. Depressed cytokine synthesis was observed in monocytes (TNF-α + ) following the provision of antigenic stimuli in vitro . These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.

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