GenoFAB

Vaccines could be one of the most powerful tools to control emerging infectious diseases. Unfortunately, recent history demonstrates that traditional vaccine development efforts started in response to the emergence of a new virus are taking much more time than most viruses need to cause disruptive epidemics.

This reactive approach needs to be replaced by a proactive strategy that makes it possible to rapidly deploy “emergency vaccines” against new infectious agents within a few weeks of their emergence. We are proposing to develop a new platform to rapidly design and produce pandemic vaccines. The process will be reproducible enough to allow public health agencies to proactively approve “emergency vaccines” developed using this process. 

The platform combines two proven vaccine technologies. It leverages a global biomanufacturing infrastructure allowing most countries to inexpensively produce the vaccines they need to protect their own populations. The vaccines will not require refrigeration during transport and storage.

Almost every country has been affected by the COVID-19 pandemic. In the span of four and half months over 4.6 million people have tested positive for SARS-CoV-2, 307,000 people have died, and the global economy is facing an unprecedented crisis that has plunged much of the world into a sudden recession.

The COVID-19 pandemic is the latest and most dramatic example of an emerging disease. It follows the 2002 SARS epidemic, the 2009 swine flu epidemic, the 2012 MERS epidemic, the 2014 Ebola epidemic, and the 2015 Zika virus epidemic. Future epidemics caused by new viruses are to be expected.  

Despite significant research investments, public authorities and pharmaceutical companies have failed to make vaccines for Zika, SARS, and MERS widely available in time to manage these outbreaks. The FDA approved an Ebola vaccine more than three years after the end of the West African epidemic.

What these failures tell us is that the traditional approach of developing vaccines is too slow. New vaccines must be available at a global scale faster than epidemics can develop, with development and mass production measured in weeks, not years.

We will develop a plug-n-play DNA molecule that, when injected into patients, will produce a safe recombinant virus carrying an antigen for SARS-CoV-2 or any other virus that will emerge in the future. This plug-n-play vaccine chassis will enable rapid design of candidate vaccines for new EIDs and should exhibit predictable safety and efficacy profiles comparable to FDA-approved vaccines.

These DNA-based vectored vaccines are much faster and easier to manufacture than other vaccines. They can be produced in bacteria in a few days using existing biomanufacturing infrastructures available in most regions of the world. We will use process automation and cybermanufacturing technologies to provide non-ambiguous descriptions of biomanufacturing processes to accelerate technology transfer to a global grid of biomanufacturing facilities. Standard workflows promote exceptional reproducibility that should allow the FDA and other regulatory agencies to approve processes for production of “emergency vaccines” that will ensure rapid response and scale up to prevent the next global pandemic.

The use of cybermanufacturing to manage a global grid of vaccine manufacturers will make it possible to produce vaccines close to where they are needed, it will be more resilient to supply chain disruptions and more scalable than a centralized vaccine production strategy.

The GenoFAB platform will ultimately benefit the populations affected by emerging infectious diseases. It will save lives. It will also limit the need for social distancing policies that negatively impact the economy and the overall wellbeing of the affected populations. However, populations will benefit from the GenoFAB platform through their governments.

Initially, GenoFAB will first develop a COVID-19 vaccine with funding from federal agencies. At the same time, it seeks to establish a partnership with a pharmaceutical company for further development and commercialization. Ultimately, the customers for the SARS-CoV-2 vaccine will be individual governments of the 227countries affected by COVID-19.

GenoFAB will later capitalize on the regulatory approval of the COVID-19 vaccine to sell an integrated platform that provides rapid response capability to the U.S. and foreign governments. Previously seen pathogens for which there are no approved treatments or vaccines are likely to resurface. This list includes other coronaviruses, the Zika virus, and a number of filoviruses causing hemorrhagic fevers. In addition, viruses affecting animals like the African Swine Fever virus could present opportunities to go through regulatory processes that might be more flexible than those applied to drugs destined for human use.  

Infectious diseases ignore geographic boundaries and national borders. They are global problems that need local solutions. Each community is responsible for the protections of its populations. Today vaccine development efforts and manufacturing capabilities are controlled by a few pharmaceutical companies located in a handful of countries. Access to vaccines is often limited and dictated by national priorities. The GenoFAB platform would provide local governments and individual countries with an avenue to rapidly access the vaccines they might to fight the next emerging virus. Making vaccines widely available is the best strategy to limit the global impact of an emerging disease.

The dominant paradigm of product development in the pharmaceutical industry is discovery, a model that is essentially based on chance. Every drug candidate is different and its approval needs to be handled individually. We are proposing a platform approach where families of new vaccines are evaluated as a whole. 

The development of the vaccine platform relies on methods from synthetic biology. Mathematical models are used to design a plug-n-play vaccine chassis. 

The manufacturing of the vaccine relies on cybermanufacturing methods, a service oriented approach to the development of distributed manufacturing processes.

The vaccine platform is based on three elements that have all been proven to work by others separately. They have never been combined but there is no obvious technological risks resulting from this combination. 

Cybermanufacturing has been used in a number of other industries but not in biomanufacturing. We have the software necessary to implement this but the performance on biomanufacturing process repeatability has yet to be characterized. 

Regulatory frameworks are the major obstacle to change in this industry. The magnitude of the COVID-19 crisis creates an unprecedented impetus for change. The FDA is pushing forward unproven vaccine technologies. Regulatory agencies of countries who do not have a strong pharmaceutical industry have proven to be less conservative than the FDA with respect to the approvals of other biologic drugs. 

The COVID-19 vaccine creates an opportunity to expedite the regulatory process and set the foundation for a new regulatory approval. Experience gained in early adopters countries will support the approval by countries with more conservative regulatory agencies. 

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Goal within a year: demonstrate the feasibility of the approach in cell cultures and animal studies. Structure a partnership with a pharma company with the resources necessary to bring the COVID19 vaccine to the market. 

Goal within 5 years: get regulatory approval for the COVID19 vaccine, develop vaccines for other emerging diseases, develop a network of contract manufacturers who could produce these vaccines on a large scale. 

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In the last 3 months 0.5 FTE. Team available to work on this project if funding when funding is available: 15. 

GenoFAB and Dr. Peccoud will leverage their extensive experience in modeling gene regulatory networks and rule-based genetic design to develop the DNA-based vectored vaccine platform. GenoFAB’s rule-based genetic design automation software has been used to design expression systems for a diversity of applications including plant expression vectors, synthetic transcription factors, microalgae expression vectors, expression vectors for expressing therapeutic antibodies in cell-free expression systems (unpublished), and biosensors based on engineered bacteriophages (unpublished).

The CSU Infectious Disease Research Center (IDRC) provides a safe, secure, state of art facility for university investigators, government scientists and industry representatives to collaboratively research the basic biology, biochemistry, molecular biology and epidemiology of bacteria and viruses that cause human and animal diseases. The IDRC has a solid track record of research in infectious diseases including development of vaccines, methods of diagnosis, and therapeutic agents for infectious agents. Colorado State University is among the world’s leaders in researching West Nile Virus, drug-resistant Tuberculosis, Yellow Fever, Dengue, Hantavirus, Plague, Tularemia and other diseases.

We are working with Colorado State University. Dr. Peccoud is Professor in the Department of Chemical & Biological Engineering at CSU where he holds the Abell Chair in Synthetic Biology. This dual affiliation makes it possible to rapidly engage different CSU faculty members who could contribute to this project. 

We will offer a service contract to governments. Governments will pay an annual fee to develop and manage a network of contract manufacturing organizations that could be mobilized rapidly. 

Combinations of grants and raising capital from investors. Financial model needs to be developed.