Design of Alphavirus Based Vaccines for Cancer
Alphavirus vectors exhibit high levels of transient heterologous gene expression and therefore possess attractive features for vaccine development. Creative Biolabs is a world leader in the field of cancer vaccine development. With our extensive experience and advanced platform, we are therefore confident in offering the best development services for alphavirus-based vaccines. We guarantee the finest results for our customers all over the world.
The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, Sindbis virus (SIN) Semliki Forest virus (SFV), and Venezuelan equine encephalitis virus (VEE). Alphavirus vectors have been used as replication-defective recombinant virus particles and have recently been used as replication-sensitive particles. Vaccination with alphavirus vectors expressing tumor antigens results in the prophylactic protection against the challenge of tumor-inducing cancer cells.
Alphaviruses
Alphaviruses are single-stranded RNA viruses with an envelope structure belonging to the family of Togaviridae. Certain alphaviruses have been associated with pathogenicity, resulting in global fever epidemics. Although this potential problem exists, several alphaviruses (SIN, SFV and VEE) have undergone engineering of vectors for heterologous gene expression and attenuated strains have been used.
Several types of vector systems have been engineered. There are three types of replication-deficient vectors:
- Naked RNA vector in vitro transcribed from plasmid DNA;
- Replication-deficient alphavirus particles generated in baby hamster kidney (BHK) cells after co-transfection of in vitro transcribed RNA from the expression and helper vectors;
- Layered DNA vector for plasmid immunization.
Fig.2 Alphavirus vector systems for vaccine delivery.
Tumor Vaccine Approaches
Alphavirus has found frequent application in the field of tumor vaccine development. Naked RNA, replication defective particles, and DNA layered vectors have been used as delivery vehicles. For example, mice have been immunized with naked SFV RNA replicons carrying the LacZ gene. A single injection of only 1 μg of SFV-LacZ RNA presented complete tumor protection. In the DNA-based tumor vaccine approaches, SIN vectors expressing mouse and human tyrosine-related protein-1 (TRP-1) were evaluated in the B16 mouse melanoma model. When mice were vaccinated five days prior to the cancer challenge, intramuscular injection was able to destroy immune tolerance and provide protection against melanoma.
Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.
Reference
- Lundstrom, K. (2017). “Alphavirus-Based Vaccines.” Methods Mol Biol 1581: 225-242.
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