Improving the safety of viral DNA vaccines: development of vectors containing both 5' and 3' homologous regulatory sequences from non-viral origin
- Authors
- Martinez-Lopez, A., Encinas, P., García-Valtanen, P., Gomez-Casado, E., Coll, J.M., and Estepa, A.
- ID
- ZDB-PUB-121004-20
- Date
- 2013
- Source
- Applied Microbiology and Biotechnology 97(7): 3007-3016 (Journal)
- Registered Authors
- Keywords
- terminators, vector regulatory sequences, fish, DNA, vaccines, plasmid, VHSV, rhabdovirus
- MeSH Terms
-
- Animals
- Antigens, Viral/biosynthesis
- Antigens, Viral/genetics
- Carps
- Disease Models, Animal
- Fish Diseases/immunology
- Fish Diseases/prevention & control*
- Fish Diseases/virology
- Gene Expression
- Genetic Vectors*
- Glycoproteins/biosynthesis
- Glycoproteins/genetics
- Hemorrhagic Septicemia, Viral/immunology
- Hemorrhagic Septicemia, Viral/prevention & control*
- Hemorrhagic Septicemia, Viral/virology
- Novirhabdovirus/genetics
- Novirhabdovirus/immunology*
- Plasmids
- Regulatory Sequences, Nucleic Acid*
- Vaccines, DNA/adverse effects*
- Vaccines, DNA/genetics
- Viral Vaccines/adverse effects*
- Viral Vaccines/genetics
- Zebrafish
- PubMed
- 23001057 Full text @ Appl. Microbiol. Biotechnol.
Although some DNA vaccines have proved to be very efficient in field trials, their authorisation still remains limited to a few countries. This is in part due to safety issues because most of them contain viral regulatory sequences to driving the expression of the encoded antigen. This is the case of the only DNA vaccine against a fish rhabdovirus (a negative ssRNA virus), authorised in Canada, despite the important economic losses that these viruses cause to aquaculture all over the world. In an attempt to solve this problem and using as a model a non-authorised, but efficient DNA vaccine against the fish rhabdovirus, viral haemorrhagic septicaemia virus (VHSV), we developed a plasmid construction containing regulatory sequences exclusively from fish origin. The result was an “all-fish vector”, named pJAC-G, containing 52 and 32 regulatory sequences of β-acting genes from carp and zebrafish, respectively. In vitro and in vivo, pJAC-G drove a successful expression of the VHSV glycoprotein G (G), the only antigen of the virus conferring in vivo protection. Furthermore, and by means of in vitro fusion assays, it was confirmed that G protein expressed from pJAC-G was fully functional. Altogether, these results suggest that DNA vaccines containing host-homologous gene regulatory sequences might be useful for developing safer DNA vaccines, while they also might be useful for basic studies.