About This Project

Ask the Scientists

What is the context of this research?

We have found the Achilles heel of all viruses. What is so unique about our approach is that our designer vaccines on the surface look IDENTICAL to the killer strain so they are extremely effective.

Our start-up is Codagenix and we have a Computer-Based technology that designs and constructs synthetic vaccines - this platform can be applied to ANY human virus.

We are currently developing a new Influenza vaccine that has multiple competitive advantages.

1t is a complete match to the target so may have higher efficacy and 2) it works at doses1,000-FOLD Lower than current vaccines in ferrets.

That means to manufacture 1,000 current flu-shot doses = one could manufacture 1,000,000 Codagenix doses, a true game changer in the field.

We have strong peer-reviewed publications in the top-scientific journals in the world (Science and Nature Biotechnology) as well a sNIH funding to support the development.

The support we seek will provide the initial funding to design and synthesize an H5N1 pandemic virus using our approach - providing a template for a future pandemic response with our ultra-low dose vaccine.

What is the significance of this project?

The 2009 pandemic highlighted the
inadequacies of the current Influenza vaccines as a means to respond to a pandemic – namely that they require large quantities of antigen/virus per dose (15ug of HA or 10^10 Influenza particles).

Nine months after the pandemic emerged, only sufficient doses (100 million) to protect 1.7% of the world’s population had been produced and most were the inactivated vaccine, which has low efficacy in high-risk populations.

This proposal seeks to move beyond the adage that we need to increase our manufacturing capabilities and source more embryonated eggs as a means to vaccine the world in the event of pandemic.

In order to provide sufficient vaccines for the globe in the event of a pandemic, the current infrastructure, making the current vaccines (at its “best case”), would take a year to yield a sufficient quantity (Collins et al., Vaccine 2009).

We present a vaccine platform capable of yielding highly immunogenic, live-attenuated influenza vaccines that are 100% antigenically to the target virus AND are capable of cross-protecting at an ultra low dose- a vaccinating dose that is 1,000-10,000 fold lower than current vaccines (Wang et al., PNAS 2013).

We have developed a rational, computer-aided approach to construct highly-efficacious live attenuated influenza virus vaccine candidates, termed Synthetic Attenuated Virus Engineering (SAVE), (Coleman et al., Science 2008). The custom attenuation via SAVE is achieved by designing hundreds of synonymous, silent nucleotide changes across the viral genome, de-optimizing the virus’s codon pair bias (Mueller et al., 2010. Nature Biotech).

This rational gene design approach allows Codagenix Inc. to maintain the amino acid sequences to be 100% identity to all viral proteins. Also maintaining a 100% amino acid sequence match to the vaccine target provides a characteristic of SAVE-attenuated vaccines that is not present in any currently available vaccine technology (Coffin J., New England Journal of Medicine 2008). SAVE-designed live attenuated influenza virus vaccine candidates have been shown to be cross-protective against heterologous challenge (Wang et al., PNAS 2013) and we have developed an ultralow-dose vaccine candidate for the clinically significant pandemic influenza strain, A/California/07/2009 (CA07). CA07 was the strain responsible for the 2009 pandemic.

What are the goals of the project?

In this proposal, we provide an inverse approach to solvng the threat of pandemic, which, if achievable, will present a new paradigm for influenza vaccinology and allow for rapid response to pandemic threats. Rather than increasing capacity – DECREASING the effective vaccine dose by 10,000 to 100,000-fold would achieve the goal of generating enough vaccine for an entire nation or globe – very cheaply and very quickly.

We believe this can only be done with a highly effective, yet very safe Live Attenuated Influenza Vaccine (LAIV). Codagenix’ core technology termed Synthetic Attenuated Virus Engineering (SAVE) is based on rational, computer-aided gene design to produce attenuated viruses through a process we call gene “deoptimization”. SAVE generates live-attenuated viruses that are 100% antigenically identical to wild type virus in all their proteins. SAVE was first developed in poliovirus (Coleman et al., 2008. Science), validated for live attenuated Influenza A vaccine candidates, (Mueller et al., 2010. Nature Biotech.), and shown to yield an Influenza A vaccine capable of protecting mice at ultra-low doses against wildtype and heterologous challenge (Yang et. al., 2013, PNAS).

In this application we seek support to apply the SAVE technology to develop a pandemic influenza vaccine program, based on SAVE-deoptimized strains that that are highly effective at ultra-low doses and thus quickly and cheaply produced when needed, rather than stockpiled.

Specifically we will pursue to following Goal: Apply the SAVE-platform to 'de-optimize' a pandemic H5N1 strain and then recover this attenuated strain from cells in culture.

Note: There is large follow-on support to test the strain recovered from this project in animals at no-cost under a contract with the National Institutes of Health. The contract covers testing of our ultra-low dose influenza vaccines in animals. We just do not have the funds to design, synthesize, and recover an ultralow dose H5N1 pandemic virus