Research Team Publishes New Methods for Synthetic Generation of Influenza Vaccines
Design Enables More Rapid Response to Potential Pandemics
LA JOLLA, CA and ROCKVILLE, MD — May 15, 2013 — A team of international researchers from the J. Craig Venter Institute (JCVI), Synthetic Genomics Inc. (SGI), Novartis Vaccines and Diagnostics, the Biomedical Advanced Research and Development Authority (BARDA, US Department of Health and Human Services), and Institut fur Virologie, Universitat, has published a study detailing new methods to rapidly generate influenza vaccine seeds by using synthetic genomics tools and technologies.
The team led by first author Philip R. Dormitzer, M.D., Ph.D., and senior authors J. Craig Venter, Ph.D., JCVI and SGI, and Rino Rappuoli, Ph.D., Novartis, published their study in the May 15 edition of the journal Science Translational Medicine. In a timed proof of conceptthis team demonstrated that in just four days and four hours they could accurately construct robust synthetic vaccine viruses for use in influenza vaccine development. The team concludes that this is a novel and accurate method that could enable a more rapid pandemic response and yield a more reliable supply of better matched seasonal and pandemic vaccines than are currently available.
"Our teams have been working hard to put our combined expertise to work toward the development of next generation vaccines," said Dr. Venter, CEO and Founder of JCVI and SGI. "We believe that synthetic genomic advances hold the key to transforming many industries and one of the most important will be in advanced vaccines that have the power to help prevent public health threats such as influenza pandemics."
The study details the synthetic vaccine techniques and methods developed by the team after the 2009 H1N1 influenza pandemic. While the response to this pandemic was the fastest in history, vaccines only became available after the rate of human infections had peaked. Novartis and other vaccine companies have relied on the World Health Organization (WHO) to identify and distribute live reference viruses or viral genes to create seasonal or pandemic vaccines. The 2010 publication of the first synthetic cell constructed by the team at JCVI described new synthetic genomic tools and techniques that were adapted to create flu vaccine viruses.
Since October 2010 Novartis, JCVI and SGI/Synthetic Genomics Vaccines Inc. (SGVI) have been working together through a BARDA-sponsored program to apply synthetic genomics tools and technologies to accelerate the production of the influenza vaccine virus strains required for vaccine manufacturing. The vaccine virus strain is the starter preparation of a virus and is the base from which larger quantities of the vaccine virus can be grown. The goal of this collaboration is to develop a "bank" of synthetically constructed vaccine viruses ready to go into production as soon as WHO identifies the flu strains. This paper outlines results of some of the first successful outcomes of this collaboration.
The researchers focused on three technological areas--speedy synthesis of DNA cassettes to produce influenza RNA genome segments, improved accuracy of rapid gene synthesis by improving error correction technology, and increased yields of hemagglutinin (HA), which is the essential vaccine antigen.
In the traditional approach to vaccine development, an influenza virus is cultured and grown in chicken eggs. The synthetic genomics approach starts with virus genome sequence data in the computer.
The team then employed synthetic genomics tools to synthesize the two antigens used in vaccine production, HA and neuraminidase (NA). To do this they developed a new cell-free gene assembly method coupled with the improved one step enzymatic error correction method for rapid and accurate gene synthesis. Although gene synthesis is now commonplace, it is still difficult to rapidly and accurately construct large pieces of DNA, large genes and whole genomes. Daniel Gibson, PH.D., and his team at SGI-DNA, along with teams at JCVI, are world leaders in the design and construction of such large gene constructs. It took the team only approximately 10 hours to construct and assemble the synthetic HA- and NA-encoding DNA cassettes ready for transfection into Madin-Darby canine kidney (MDCK) cells. This method enables the rapid and accurate conversion of digital sequence information to biologically active DNA. This is one of the key differences in synthetically derived vaccines versus traditionally developed vaccines.
The next step developed and described by the team involves rescuing the vaccine virus from the manufacturing cell line. The team employed a novel method of using one cell line for both seed generation and vaccine antigen production. This adds to the efficiency of the new vaccine production and alleviates some of the regulatory and manufacturing complexity.
"As an industry leader in the research, development, manufacture and supply of flu vaccines, Novartis is committed to identifying new ways to speed development of safe and efficacious vaccines to protect patients from seasonal flu and potential pandemics," said Rino Rappuoli, Head, Vaccines Research, Novartis Vaccines and Diagnostics. "Our research shows the potential power of synthetic vaccine development in addressing emerging public health threats. By electronically transmitting genetic information rather shipping biological materials, we can begin development of new vaccines more quickly, and ultimately, better protect global health."
This work was made possible in part through a contract from BARDA and funds from the Novartis Foundation. Funding also came from the National Institutes of Health National Institute of Allergy and Infectious Diseases.
SGI through subsidiaries, SGVI and SGI-DNA, has continued to develop new technologies to rapidly and accurately synthesize genes and genomes of any size. JCVI scientists along with researchers at the National Center for Biotechnology Information (NCBI) and 44 academic institutions recently announced that they had sequenced and published more than 10,000 influenza virus genomes as part of the Influenza Virus Genome Sequencing Project (IGSP) of the National Institute of Allergy and Infectious Diseases (NIAID). JCVI scientists have sequenced approximately 75 percent of the influenza virus genomes available in GenBank. Novartis has been working with JCVI for more than a decade to apply their findings in the genomics field to develop novel vaccines that prevent disease. The last collaboration introduced the use of genomics in vaccines research, a technology today known as "reverse vaccinology."
The JCVI is a not-for-profit research institute in Rockville, MD and San Diego, CA dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 300 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org.
About Synthetic Genomics Inc.
SGI, a privately held company founded in 2005, is dedicated to developing and commercializing genomic-driven solutions to address a wide range of global challenges. The company is focused on several key research and business programs including: developing new synthetic DNA products and technologies through its subsidiary, SGI-DNA; algae biofuels; new and improved food and nutritional products; and clean water technology. SGI is also involved in synthetically derived vaccine development through Synthetic Genomic Vaccines Inc. (SGVI), a business unit co-founded with the J. Craig Venter Institute; and in developing sustainable crops such as castor and sweet sorghum and agricultural products through AgraCast, a company co-founded with Plenus S.A. de C.V. For more information go to: www.syntheticgenomics.com.