Improved efficacy of a gene optimised adenovirus-based vaccine for venezuelan equine encephalitis virus.
BACKGROUND
Optimisation of genes has been shown to be beneficial for expression of proteins in a range of applications. Optimisation has increased protein expression levels through improved codon usage of the genes and an increase in levels of messenger RNA. We have applied this to an adenovirus (ad)-based vaccine encoding structural proteins (E3-E2-6K) of Venezuelan equine encephalitis virus (VEEV).


RESULTS
Following administration of this vaccine to Balb/c mice, an approximately ten-fold increase in antibody response was elicited and increased protective efficacy compared to an ad-based vaccine containing non-optimised genes was observed after challenge.


CONCLUSIONS
This study, in which the utility of optimising genes encoding the structural proteins of VEEV is demonstrated for the first time, informs us that including optimised genes in gene-based vaccines for VEEV is essential to obtain maximum immunogenicity and protective efficacy.
Williams
Amanda J
AJ
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 OJQ, UK. ajwilliams@dstl.gov.uk
O'Brien
Lyn M
LM
Phillpotts
Robert J
RJ
Perkins
Stuart D
SD
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D003062:Codon; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016019:Survival Analysis; D015678:Viral Structural Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D003062:Codon; D007074:Immunoglobulin G; D015678:Viral Structural Proteins; D014765:Viral Vaccines