Codagenix attracts DOD funding for synthetic biology approach to dengue vaccine

Codagenix’s synthetic biology approach to a vaccine for dengue, a mosquito-borne viral disease, has received a $4.4 million award from the US Department of Defense. Almost half of people live in areas with a risk of dengue, and about 100 million people become sick every year, according to the US Centers for Disease Control and Prevention. Dengue has historically put many troops out of commission and continues to pose a significant health risk to military members deployed in dengue-endemic areas, but the nature of the disease has made vaccination development challenging.

There are four related groups, or serotypes, of dengue virus that cause the disease. Infection with one serotype causes long-term immunity to that type, but it also makes subsequent infections with other types worse. In a process called antibody-dependent enhancement (ADE), antibodies bind to the virus, but instead of fighting it, they help it invade more cells. In order to prevent ADE, a dengue vaccine needs to be equally protective against all four types.

“Vaccine development is hard against one virus. Now you have to do all four simultaneously,” Codagenix CEO J. Robert Coleman says.

A jab also has to offer balanced protection against the four virus types so that the vaccine itself doesn’t cause ADE the first time someone encounters a serotype of the virus in the real world. This likely occurred in several people vaccinated with Sanofi’s Dengvaxia, which was administered to about 800,000 children in the Philippines in 2016 and 2017. It was approved by the US Food and Drug Administration in 2019, but only for children who have had a previous infection.

Being able to balance all four serotypes, Coleman says, is where Codagenix’s technology stands out. Lots of dengue vaccines, including Codagenix’s, are made using live attenuated viruses, or live copies of the virus that have been weakened and therefore can’t cause harm. Often, the viruses are weakened through a process called passaging, which introduces the virus into a host or series of hosts where it isn’t as good at replicating; the virus adapts to the new hosts, becoming less virulent to humans.

Codagenix’s vaccine platform, on the other hand, is based on codon deoptimization. A codon is a string of three nucleotides that either represents the code for an amino acid in a given gene’s corresponding protein or acts as a signal to stop protein synthesis. Codagenix uses an algorithm that can recode the genetic material of a virus, inserting codons that slow down the translation rate. Their vaccine includes all four serotypes that have been attenuated this way.

But Codagenix’s approach doesn’t guarantee balanced protection against all four serotypes, says Kathryn Hanley, a virus expert at New Mexico State University who is an inventor of an US National Institutes of Health–backed dengue vaccine that uses what’s called a chimeric approach. “Getting those deoptimized viruses to give a balanced response is going to be just as difficult as with any other chimeric or any other live vaccine approach,” she says. “I think there’s a little bit of oversell there, in the idea that you can rationally balance these responses.” Coleman says that in primate studies done to date, his company’s approach results in a balanced response.

Days after the announcement of the DOD funding for Codagenix, Takeda Pharmaceutical’s dengue vaccine saw its first approval Aug. 22 in Indonesia. That vaccine also uses a chimeric approach: in Takeda’s case they use one type of attenuated virus as a base and make versions of it with genes swapped in from all the other types, creating a cocktail that aims to trigger an equal immune response to all serotypes. For Codagenix’s approach, which includes codon-modified versions of each of the four whole viruses, Coleman says the company is aiming to submit an Investigational New Drug application to the FDA next year.