2). In this case, the mechanism of protection is believed to be dependent on antibodies recognizing NS1 that bind to cell surface-associated NS1 and facilitate phagocytosis and clearance of infected cells through

Fc-γ receptors [36]. NS1 has therefore been proposed as a component of new flavivirus vaccines [48] and [49]. All flaviviruses are antigenically related, as originally shown in hemagglutination-inhibition tests with polyclonal sera [50] but as also revealed in ELISA. Cross-neutralization, however, is confined to more closely related flaviviruses that have been grouped into so-called serocomplexes [51] (Fig. 3). The minimum amino acid sequence identity in the E protein of all flaviviruses Sorafenib ic50 is 40–44% and within serocomplexes it is 60–70. Although cross-neutralization and cross-protection are observed within serocomplexes, its extent and duration are strongly dependent on the degree of amino acid similarity in E. For instance,

infection with any one of the four DENV serotypes induces life-long protection against the same serotype but only for few months against the other serotypes [6]. The epitopes recognized by broadly cross-reactive antibodies have Dinaciclib supplier been mapped to the fusion peptide loop at the tip of DII [39], [44], [45] and [52] (Fig. 1) which is highly conserved among all flaviviruses. Because of the cryptic nature of this epitope in the context of mature virions, such antibodies usually do not contribute to virus

neutralization [52] and [53]. The accessibility of the fusion loop, however, may be higher in partially immature virions [53] and [54] that are infectious and released in significant amounts by DENV-infected cells [55]. ADAMTS5 FP-specific antibodies may therefore contribute to neutralization of partially immature infectious viruses. The development of the YFV 17D live-attenuated vaccine was a landmark in the history of viral vaccines, and in 1951 Max Theiler was awarded the Nobel prize in Medicine for his achievements in attenuating the wild-type virus by serial passaging in mouse and chicken tissue [3]. Since its development in 1937, more than 500 million people have been vaccinated and over 98% of vaccinees are believed to be protected for at least 10 years [56]. Despite its great record in protecting from YF, evidence for a significant degree of severe vaccine-associated adverse events has been accumulating in the last ten years. These include YF vaccine-associated viscerotropic disease and YF vaccine-associated neurotropic disease (with a higher incidence in elderly and immunocompromised individuals) at a rate exceeding that of other live virus vaccinations [56] and [57]. Also, due to a largely unchanged manufacturing process since 1945, the vaccine contains substantial amounts of chicken embryo proteins, and allergic reactions contribute to the adverse events observed with its use [56].