Synthetic Influenza Virus May Cut Vaccine Delivery Time

Jenni Laidman

May 16, 2013

Vaccines against pandemic influenza may reach the field faster if the virus' genetic sequence is posted immediately to the Internet and used as a template for influenza virus gene assembly and vaccine creation, according to an article published in the May 15 issue of Science Translational Medicine.

Philip R. Dormitzer, MD, PhD, global head of virology and head of research in the United States for Novartis Vaccines and Diagnostics, Cambridge, Massachusetts, and colleagues developed a method that skips a time-consuming step in traditional vaccine production. Typically, the influenza virus must be grown and then shipped to various laboratories, which grow it in chicken eggs to produce the vaccine. Using the traditional method, vaccine manufacturers put a vaccine in the field faster than ever during the 2009 H1N1 influenza pandemic. Yet even with the record 6-month turnaround it took to distribute millions of vaccine doses, the second wave of the pandemic had already passed before the vaccine was widely available.

In the current study, Dr. Dormitzer and colleagues worked from the hemagglutinin and neuraminidase virus sequences of an unidentified virus and used enzymes to make the viral DNA sequences. The group had a vaccine virus in hand by the end of the week. The synthetic virus sequence was confirmed by the Centers for Disease Control and Prevention, and the virus was tested in ferrets, where it triggered the proper immune response. Ferrets are the most commonly used mammalian model for human influenza. The virus the team used turned out to be a strain of H7N9.

"If laboratory demonstrations of synthetic vaccine technology such as that reported here prove themselves in manufacturing and field implementation before the next pandemic, a high-yielding vaccine virus could be available to manufacturers for testing, scale-up, and process optimization days, not months, after a new virus is first detected," the authors write.

"These innovations in production are very welcome, really interesting, and promising," John Treanor, MD, chief of the Infectious Disease Division, University of Rochester Medical Center, New York, told Medscape Medical News. Dr. Treanor was not involved in the study.

"Realistically, though, we're always going to be faced with this race against time," he continued. "This moves us in the right direction. By itself, it's not going to solve the problem. There are several other components that take a lot of time."

The authors also used the process described in the article to generate other viral strains, including H1N1, seasonal H3N2, swine-origin H3N2v, B, attenuated H5N1, and H7N9 strains. "To date, we have not encountered any influenza virus strain that cannot be rescued synthetically," the authors write.

In the 2009 outbreak, with the record vaccine turn-around, Novartis Vaccines and Diagnostics used recombinant methods to make a potential vaccine, completing the work in 11 days. Eighteen days later, it received the vaccine virus made the traditional way from the World Health Organization. Regulatory hurdles prevented the use of the Novartis recombinant vaccine.

Novartis Vaccines and Diagnostics, the J. Craig Venter Institute, Synthetic Genomics Vaccines, and the Biomedical Advanced Research and Development Authority, US Department of Health and Human Services collaborated on the newly reported research.

Several of the authors are employees or contractors with Novartis Vaccines and Diagnostics and/or Novartis shareholders. Dr. Treanor serves on an unrelated scientific advisory board for Novartis.

Sci Transl Med. 2013;5:185ra68. Abstract


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