Gene synthesis is routinely used in vaccine research, from basic studies in immunology and microbiology that are critical for rational vaccine design, to cutting-edge DNA vaccine drug development efforts. New vaccines are needed to control emerging threats such as Ebola Virus as well as persistent infectious viruses such as seasonal Influenza A. Cancer Vaccines can act both prophylactically to prevent infection by oncogenic viruses and therapeutically to stimulate an immune attack on tumors.

Vaccine design studies can benefit from the unique advantages offered by Gene Synthesis. For example, codon optimization can be harnessed in different ways for different types of vaccine research and development:

• Codon optimization of genes encoding antigenic proteins can allow high-level antigen expression to stimulate the immune system without introducing the entire microbial pathogen, as in DNA vaccines.¹
• DNA vaccine-induced immunity can be enhanced by the co-delivery of codon-optimized synthetic genes that encode molecular adjuvants.
• Codon-deoptimization of critical genes in viruses can be used to protect against viral infections such as Influenza A.²
• Codon optimization makes it easier to express and purify antibodies that recognize key viral protein, which can be used as therapeutic antibodies or in basic research applications. For example, an antibody that binds an antigenic protein can aid in determining its crystal structures or in performing other biophysical or biochemical assay. Gaining a better understanding of antigens can help to enable rational design of antigens to develop better vaccines for infectious diseases such as respiratory syncytial virus (RSV).³

For DNA vaccine development, gene synthesis can be used to construct gene cassettes that drive expression of specific antigenic proteins, codon-optimized synthetic genes encoding adjuvants, and specialized vectors optimized for safety. Gene synthesis is also used extensively in basic virology and microbiology research to understand mechanisms of how infection occurs and how the immune system responds to specific pathogens.

References

1. Shedlock et al. Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity. Vaccines. 2014 Feb; 196-215.
2. Nogales et al., Influenza A Virus Attenuation by Codon Deoptimization of the NS Gene for Vaccine Development J. Virol. 2014 Sep 15;88(18):10525-40.
3. McLellan et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340, 1113–1117 (2013).

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