Synthetic Biology Approaches for Vaccine Development

Abstract

Several approaches to vaccine design exist, including inactivated and live attenuated vaccines. Live attenuated vaccines tend to promote longlasting immunity by activating both cellular and antibody responses. By taking advantage of technologies developed in synthetic biology, attenuated polioviruses and influenza viruses have been synthesized and shown to protect susceptible mice from infection. The live attenuation of these viruses was achieved by a novel approach to vaccine design, synthetic attenuated virus engineering (SAVE), in which changes to the preferential usage of certain codons and codon pairs to encode amino acids and adjacent amino acid pairs have been incorporated into the virus during synthesis. By choosing the extent of under-represented codons or codon pairs incorporated (which also results in a concomitant increase of rare CpG and UpA dinucleotide frequencies), viruses can be attenuated in both cell culture and mouse models in a tunable fashion. This approach has been extended to HIV retroviruses and the bacterium, Streptococcus pneumonia. With the increased pace of advance in vaccine designs, a view that includes disease eradication rather than just control is advocated. With initial positive results in viral attenuation using SAVE, investigations in other virus families may show SAVE to have a broad applicability. Keywords: codon usage (also referred to frequently as “codon bias”); codon pair bias (CPB); shuffling/scrambling; synthetic attenuated virus engineering (SAVE); deoptimization