A machine learning-aided algorithm meticulously guides this process, ensuring the modifications are safe and effective. “We recode the DNA of a virus to slow down the rate of translation in the human host cell,” said J. Robert Coleman, the co-founder and CEO of Codagenix.
All viruses use the body to replicate themselves. “They want to come in and make a trillion copies of themselves in eight hours,” said Coleman, a trained virologist. “We’ve found a way to recode their genetic material to slow that process down.”
The scientists at Codagenix introduce hundreds of modifications to prevent viruses from reverting — a longstanding concern with conventional live vaccines, as Coleman noted. “Our platform enables us to make a single change, test that change and see if it results in the desired level of attenuation,” he added.
Codagenix sees expanding horizons in vaccine development
Codagenix, partnering with the Serum Institute of India, began dosing an international phase 3 clinical trial for CoviLiv, a live-attenuated, intranasal COVID-19 vaccine in October 2022. The study is part of the World Health Organization’s Solidarity trial vaccines initiative, which seeks to support the development of second-generation COVID-19 vaccines. Codagenix’s CoviLiv vaccine expresses all SARS-CoV-2 proteins, not just the spike protein as the mRNA vaccines do. The design potentially increases efficacy against variants, Coleman said.
Preliminary clinical data demonstrated that CoviLiv is well tolerated, immunogenic and induced broad cellular immunity against known SARS-CoV-2 variants. The trial will involve up to 20,000 healthy adults in regions with low vaccination rates. Another ongoing U.K.-based phase 1 trial is exploring CoviLiv as an intranasal booster for people who were vaccinated with mRNA or adenovirus-vectored COVID-19 vaccines.
Codagenix’s focus also extends beyond COVID-19. The company’s vaccines for respiratory syncytial virus (RSV) and influenza are now in phase 1 trials. Its flu vaccine, which is live attenuated and injectable, has shown promise in preclinical studies, holding up against multiple flu strains. The company hopes to confirm these effects in human trials. For RSV, Codagenix intends to develop vaccines for both pediatric and adult populations. “Both our influenza and RSV vaccines have shown promising results, and we’re eager to further validate these in upcoming trials,” Coleman said.
The unique advantage of live-attenuated vaccines
Codagenix’s live-attenuated vaccines could potentially offer unique advantages over mRNA vaccines, currently the most prevalent type for SARS-CoV-2. These vaccines are engineered to “mimic natural infection,” stimulating a comprehensive immune response that not only targets antibodies but also stimulates mucosal antibodies and T-cell immunity.
“Whether it’s our COVID vaccine or flu vaccine, they elicit not just antibodies but also T cells,” Coleman points out. Such a holistic immune response means that recipients of Codagenix’s vaccines experience an immune reaction similar to a natural infection, but without the disease symptoms.
Another strength of live-attenuated vaccines lies in their resilience against viral mutation or “drift.” “If the immune response is solely focused on producing antibodies, the virus is pressured to mutate,” Coleman explained. “The virus is always somewhat drifting, and we’re continually trying to develop antibodies that can keep pace.” This drift is less problematic for T-cell immunity, which is more stable and potent, providing a wider and more long-lasting immune response.
Codagenix’s approach to live-attenuated vaccine design hinges on introducing a copious amount of small mutations, which collectively create a significant effect, akin to the concept of “death by a thousand cuts.” “When we introduce our codon changes, for example, with our COVID vaccine, we have 293 mutations, each contributing a small additive effect,” Coleman explains. “Even if the virus could reverse one mutation, it lacks the strength to simultaneously reverse all 293.”
Coleman shared a promising data point from a phase 1 study of its SARS-CoV-2 vaccine. “We gave our vaccine to participants in early 2021, collected their T cells and waited an entire 18 months for the virus to mutate in the real world,” Coleman explained. In late 2022, they introduced these previously isolated T cells to the omicron variant of the virus. Not only did these cells show resistance, but “our data showed that these vaccinated individuals had actually developed an immune response against omicron before the strain even existed.” The data suggest that its nasally-delivered, live-attenuated vaccine could elicit a broad and pre-emptive immune response, preparing the body to combat future versions of the virus.
The journey ahead
Codagenix is set on a fast-paced trajectory in vaccine development. “We can transition from synthetic genetic material to a fully replicating variant version of our vaccine in 18 days,” Coleman said. He also noted that Codagenix, despite being a relatively small company, was able to follow closely behind Big Pharma giant Pfizer in their vaccine development partnership with BioNTech. “We could actually challenge Moderna,” Coleman added.
Finally, Codagenix’s vaccines are dose-sparing. Unlike mRNA vaccines, which require the construction of every molecule, live vaccines use traditional manufacturing methods, self-amplifying to produce hundreds of doses per milliliter. “We had to learn how to manipulate coronavirus during a pandemic,” Coleman reflected. “And we’re rolling really fast now.”
Filed Under: clinical trials, Drug Discovery, Drug Discovery and Development, Infectious Disease, machine learning and AI
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