Effective vaccines are also available for the immunoprophylaxis HA-1077 nmr of Japanese encephalitis, including both inactivated whole virus and live attenuated vaccines. Originally, the substrates for inactivated vaccines were either infected mouse brains or primary hamster kidney cells (China) and vaccine efficacies

of 76–95% were reported [9]. Recently, a new inactivated vaccine was developed by Intercell (IXIARO) that is based on the attenuated SA14-14-2 strain grown in Vero cells [59]. Several studies have demonstrated excellent immunogenicity, tolerability as well as non-inferiority to mouse brain-derived inactivated vaccines and this product is now available on the market in many countries, including the US, Europe, Japan, and Australia [60], [61] and [62]. The attenuated SA-14-14-2 strain was developed in China and is licensed in this country as a live vaccine since 1988 [9]. The field effectiveness is comparable to that of the inactivated vaccines (88–96%) and

more than 300 million doses have been administered since its licensure [9]. A new generation live JE vaccine was developed by Sanofi Pasteur that is based on a chimeric virus containing the prM and E proteins (Fig. 4) of JEV whereas all of the rest is derived from the attenuated YFV 17D strain as a backbone (Chimerivax/IMOJEV) [63]. Clinical studies revealed excellent immunogenicity INCB28060 without safety concerns and the vaccine is now licensed in Australia [64]. TBE can be effectively prevented by highly purified inactivated whole virus vaccines that are produced in Europe and Russia, using primary chicken embryo cells as a substrate [11], [65] and [66]. Their use in endemic regions differs widely, with the highest vaccination coverages reached in Austria (85%) [67] and the Sverdlovsk district of Russia (81%) [68]. The field effectiveness of both the European and Russian vaccine is very high. It reaches 98% [67] and [68] when the proper vaccination schedule is applied and has led to a dramatic decline of disease incidence in the vaccinated population. The dengue serocomplex of

flaviviruses consists of 4 serotypes (Fig. 3), each of which is made up Thiamine-diphosphate kinase of several genotypes [69]. Consistent with substantial differences in the amino acid sequence of their E proteins, the degree of cross-neutralization and cross-protection between members of different serotypes is limited. After human infection with one serotype, heterologous protection lasts only for few months and epidemiological observations indicate that previous infection with one serotype can predispose to the severe forms of dengue (DHS/DSS) upon re-infection by another serotype [70]. Since endemic regions with co-circulating different serotypes have enormously expanded (establishment of hyperendemic areas) also the incidence of DHF/DSS has increased dramatically in the last decades [5] and [71].