J Stephenson1. 1. London School of Hygiene and Tropical Medicine, Division of Infectious and Tropical Medicine, UK. j.stephenson@wellcome.ac.uk
Abstract
BACKGROUND: Vaccines against many flaviviruses, such as Japanese encephalitis virus (JEV), yellow fever virus (YFV) and tick-borne encephalitis virus (TBEV), have been successfully used for many years. Other diseases such as dengue fever (DF) and hepatitis C are still major public health problems as no licensed vaccines are in use. OBJECTIVES: To review studies on the use of defective recombinant adenoviruses (Rads) as experimental flavivirus vaccines and comment on their use to prevent infections with other members of the Flaviviridae such as hepatitis C virus. STUDY DESIGN: Recombinant adenoviruses, defective in their replication strategy, contain deletions in the E1 and E3 regions of the genome to increase the amount of foreign genetic material that can be inserted. The expression of foreign genes, inserted into these regions, can be driven by the adenovirus's own promoter, or by an additional viral promoters. CONCLUSIONS: Rads have been successfully used to raise protective immunity in experimental models of infection with several viruses. They can elicit both humoral and cell-mediated immunity and can be given parenterally or by oral administration. In addition, their hepatotropism makes them suitable for tackling diseases such as hepatitis C. Careful design of the vaccine vectors is advised to ensure their efficacy and safety, and as hepatitis C is a persistent infection, it may be advisable to design Rads containing genes encoding for non-structural proteins in preference to structural proteins.
BACKGROUND: Vaccines against many flaviviruses, such as Japanese encephalitis virus (JEV), yellow fever virus (YFV) and tick-borne encephalitis virus (TBEV), have been successfully used for many years. Other diseases such as dengue fever (DF) and hepatitis C are still major public health problems as no licensed vaccines are in use. OBJECTIVES: To review studies on the use of defective recombinant adenoviruses (Rads) as experimental flavivirus vaccines and comment on their use to prevent infections with other members of the Flaviviridae such as hepatitis C virus. STUDY DESIGN: Recombinant adenoviruses, defective in their replication strategy, contain deletions in the E1 and E3 regions of the genome to increase the amount of foreign genetic material that can be inserted. The expression of foreign genes, inserted into these regions, can be driven by the adenovirus's own promoter, or by an additional viral promoters. CONCLUSIONS: Rads have been successfully used to raise protective immunity in experimental models of infection with several viruses. They can elicit both humoral and cell-mediated immunity and can be given parenterally or by oral administration. In addition, their hepatotropism makes them suitable for tackling diseases such as hepatitis C. Careful design of the vaccine vectors is advised to ensure their efficacy and safety, and as hepatitis C is a persistent infection, it may be advisable to design Rads containing genes encoding for non-structural proteins in preference to structural proteins.
Authors: Claudia Marcela Diaz; Alberto Chiappori; Luigi Aurisicchio; Ansuman Bagchi; Jason Clark; Sheri Dubey; Arthur Fridman; Jesus C Fabregas; John Marshall; Elisa Scarselli; Nicola La Monica; Gennaro Ciliberto; Alberto J Montero Journal: J Transl Med Date: 2013-03-08 Impact factor: 5.531