Re-Writing Vaccine Development
For decades, live attenuated viruses, that is, viruses that have been damaged or otherwise altered in order to cause an immune response but not disease) were behind many of the world’s most effective and important immunizations, including major public health victories such as the global control of horrible infectious diseases such as measles, yellow fever, and polio. Our bodies’ immune systems typically react best to vaccines that are most similar to the target pathogen; these weakened versions of the wild-type virus tend to induce the production of antibodies and other cellular defenses that are likely to protect us from the natural pathogen if we are unlucky enough to be exposed in day-to-day life.
Traditional live vaccines, however, have a number of imperfections, including that they can revert to virulence, that they necessitate challenging and antiquated manufacturing processes in many cases, and, most importantly, can require in the context of pandemic threats, long and expensive development timelines. Many live vaccines were developed as a result of “random point mutations to achieve attenuation. This means as few as five nucleotide changes can be achieved through unpredictable mutation-forcing techniques such as repeat passaging under sub-optimal conditions (e.g., under low temperatures or in an inefficient growth medium). While this approach worked well for some of the earliest commercial-scale vaccines, emerging supply and safety issues beg the question: can we make better vaccines?
Here’s where codon deoptimization can offer a vast improvement. Codagenix flips the live vaccine paradigm on its head, leveraging computational approaches and the rapidly falling cost of DNA synthesis to design live vaccines attenuated by increasing the number of less efficient codons. Because these vaccines are based on wild type genomes, they are easier to manufacture and more genetically stable than traditional live vaccines. Importantly, Codagenix’s approach allows it to develop entirely new vaccine candidates in a matter of months as opposed to years. Codagenix can order custom, deoptimized viral genomes and enter manufacturability and early animal testing in a number of weeks.