Fig. 4.

Butantan/NIH recombinant attenuated vaccine strategy for dengue. The upper diagram shows schematically the strategy used by the Butantan, in cooperation with the US National Institutes of Health (NIH), to develop a second-generation recombinant Dengue vaccine. The Dengue virus genome is about 11,000 bases of positive-sense, single stranded RNA (ssRNA) that codes for three structural proteins (capsid protein C, membrane protein M, envelope protein E) and seven nonstructural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5). It also includes short non-coding regions on both the 5′ and 3′ ends (black lines). The vaccine constructs comprise three full-length dengue viruses types 1, 3, 4 (depicted in blue, green and red in the lower diagram), attenuated by one or more 30-nucleotide deletions in the 3′ untranslated region (NS1 to NS5). The non-structural proteins are derived from type-1, type-3, and type-4 vaccines. The type-2 component is a chimeric virus, carrying virus type 2 structural M and E genes and capsid and non-structural genes of virus type 4 genome. Abbreviations: DENV-1: Dengue virus type 1; DENV-2: Dengue virus type 2; DENV-3: Dengue virus type 3; DENV-4: Dengue virus type 4. NS = non structural genes (Figure courtesy of A. Precioso). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)