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.
Conclusion: 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.
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http://dx.doi.org/10.1186/1743-422X-6-118 | DOI Listing |
Microorganisms
November 2024
Biology Department, University of Puerto Rico-Rio Piedras, San Juan 00931, Puerto Rico.
'Frozen' virus genome sequences are sampled from outbreaks and have unusually low sequence divergence when compared to genome sequences from historical strains. A growing number of 'frozen' virus genome sequences are being reported as virus genome sequencing becomes more common. Examples of 'frozen' sequences include the 1977 H1N1 'Russian' flu; Venezuelan Equine Encephalitis Virus from Venezuela and Colombia in 1995; E71 sequences from a Hand, Foot and Mouth outbreak in 2007-2009 in China; and a polio strain isolated in 2014 from Anhui, China.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Department of Infectious Disease, Imperial College London, London W2 1PG, UK.
Self-amplifying RNA (saRNA) is an extremely promising platform because it can produce more protein for less RNA. We used a sort and sequence approach to identify host cell factors associated with transgene expression from saRNA; the hypothesis was that cells with different expression levels would have different transcriptomes. We tested this in CDK4/hTERT immortalized human muscle cells transfected with Venezuelan equine encephalitis virus (VEEV)-derived saRNA encoding GFP.
View Article and Find Full Text PDFFront Immunol
January 2025
Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, United States.
Neurotropic alphaviruses such as Venezuelan equine encephalitis virus (VEEV) are critical human pathogens that continually expand to naïve populations and for which there are no licensed vaccines or therapeutics. VEEV is highly infectious via the aerosol route and is a recognized weaponizable biothreat that causes neurological disease in humans. The neuropathology of VEEV has been attributed to an inflammatory immune response in the brain yet the underlying mechanisms and specific immune cell populations involved are not fully elucidated.
View Article and Find Full Text PDFMol Ther
December 2024
Michael Smith Laboratories, University of British Columbia, Vancouver, Canada V6T1Z4; School of Biomedical Engineering, University of British Columbia, Vancouver, Canada V6T1Z4. Electronic address:
Self-amplifying RNA (saRNA) vectors are a next-generation RNA technology that extends the expression of heterologous genes. Clinical trials have shown the dose-sparing capacity of saRNA vectors in a vaccine context compared to conventional messenger RNA. However, saRNA vectors have historically been based on a limited number of alphaviruses, and only the Venezuelan equine encephalitis virus-based saRNA vaccines have been used clinically.
View Article and Find Full Text PDFACS Infect Dis
December 2024
Chemistry and Biotechnology Science and Engineering Program, College of Science, The University of Alabama in Huntsville, Huntsville, Alabama 35899, United States.
New World alphaviruses, including Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that cause disease in humans. These viruses are endemic to the western hemisphere, and disease in humans may lead to encephalitis and long-term neurological sequelae. There are currently no FDA-approved vaccines or antiviral therapeutics available for the prevention or treatment of diseases caused by these viruses.
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