The yellow fever 17D virus as a platform for new live attenuated vaccines

Abstract

The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

Keywords: Yellow Fever 17D virus-vaccines-immune responses-expression vector-insertion sites-live recombinant.

Figure 1. Insertion of heterologous sequences into the YF 17D genome. (A) YF genome is composed of a single positive single-stranded RNA containing 10 862 nucleotides. The major portion of the genome consists of an open reading frame flanked by a 5` and 3` untranslated region. The heterologous sequence insertion sites that have been described so far for recovering recombinant YF virus are indicated by a red arrow; (B) The translation of this large ORF produces a precursor polyprotein of 3411 amino acid residues, which are mainly co- and post-translationally processed at specific sites by the viral NS2B-NS3 proteolytic complex (white arrows) and signal peptidase (black arrows) producing the virion (structural proteins) and replicase elements (non-structural proteins). (C) Topological arrangement of YF proteins and the regions in which were possible to express heterologous sequences, indicated by red arrows. On the cytoplasmatic side, the viral proteins are processed by the viral NS2B/NS3 proteolytic complex (white arrows) whereas on the ER side by signal peptidases, furin, and an unknown protease that cleaves the carboxi-terminus of NS1.