Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics

  title={Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics},
  author={Philip R. Dormitzer and Pirada Suphaphiphat and Daniel G. Gibson and David E. Wentworth and Timothy B. Stockwell and Mikkel A. Algire and Nina Alperovich and Mario Barro and David M Brown and Stewart P. Craig and Brian M. Dattilo and Evgeniya A. Denisova and Ivna P. de Souza and Markus Eickmann and Vivien G. Dugan and Annette Ferrari and Ra{\'u}l C. Gomila and Liqun Han and Casey Judge and S. G. Mane and Mikhail Matrosovich and Chuck Merryman and Giuseppe Palladino and Gene A. Palmer and Terika Spencer and Thomas Strecker and Heidi Trusheim and Jennifer Uhlendorff and Yingxia Wen and Anthony Yee and Jayshree Zaveri and Bin Zhou and Stephan Becker and Armen M. Donabedian and Peter W. Mason and John I. Glass and Rino Rappuoli and J. Craig Venter},
  journal={Science Translational Medicine},
  pages={185ra68 - 185ra68}
Synthesis of viral genes from sequence information allows rapid generation of influenza vaccine viruses, facilitating rapid responses to influenza pandemics. Fast, Faster, Fastest Unlike the public health successes of polio and smallpox vaccines, the flu vaccine has not been so effective. Part of the reason is that there are thousands of influenza virus strains and they evolve rapidly, even to the point of switching hosts, most alarmingly from animals to humans. To keep up with this ever… 

Rapid production of synthetic influenza vaccines.

  • P. Dormitzer
  • Biology, Medicine
    Current topics in microbiology and immunology
  • 2015
Novartis has developed a synthetic approach to influenza vaccine virus generation that resulted in the production, clinical testing, and stockpiling of an H7N9 vaccine before the second wave of the outbreak struck at the end of 2013.

Pandemics Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to

The authors show that their new procedure could be similar to the one that has recently killed numerous people in China −− sequence and designing more productive vaccine viruses, and streamlined the process considerably by synthesizing the genes needed for the vaccine directly from the et al.

Bringing influenza vaccines into the 21st century

Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses.

Rapidly produced SAM® vaccine against H7N9 influenza is immunogenic in mice

If the SAM vaccine platform proves safe, potent, well tolerated and effective in humans, fully synthetic vaccine technologies could provide unparalleled speed of response to stem the initial wave of influenza outbreaks, allowing first availability of a vaccine candidate days after the discovery of a new virus.

Vaccine strain selection for influenza A viruses is complicated by unique pre-exposure histories and rapid mutation of glycoproteins

This dissertation investigates multiple factors associated with surveillance and vaccine strain selection that could be improved to produce more reliable and effective seasonal influenza vaccines and proposes the implementation of “sequence-first” surveillance, new cell culture systems, and the use of clinical human antisera for antigenic characterization of viruses will improve the process of selecting seasonal influenza vaccine strains.

Novel Platforms for the Development of a Universal Influenza Vaccine

The development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines.

Influenza Vaccines: A Moving Interdisciplinary Field

Adjuvants and universal vaccines can target immune responses to more conserved influenza epitopes, which eventually will result in broader protection for a longer time, and may shorten the time gap between emergence of a new influenza virus and a vaccine becoming available.

A paradigm shift in vaccine production for pandemic influenza.

  • J. Steel
  • Biology
    Annals of translational medicine
  • 2015
If the H7N9 virus were to acquire the ability to transmit efficiently in humans, its subsequent emergence into an immunologically naive population would likely require a major global public health response.

Design of alternative live attenuated influenza virus vaccines.

This chapter describes experimental vaccine generation and production strategies that address the deficiencies in current methods for potential human and agricultural use.

Current and future influenza vaccines

An overview of current vaccine options is provided and efforts directed toward the development of next-generation vaccines are described, including closer monitoring of viral evolution.



Generation of High-Yielding Influenza A Viruses in African Green Monkey Kidney (Vero) Cells by Reverse Genetics

Improved properties were mediated by the substitution of the PR8 NS gene for that of a Vero-adapted reassortant virus, and pave the way for the reproducible generation of high-yielding human and animal influenza vaccines by reverse genetics methods.

Gene Constellation of Influenza A Virus Reassortants with High Growth Phenotype Prepared as Seed Candidates for Vaccine Production

The parental origin of the remaining six genes encoding the internal proteins that contribute to the hy phenotype in ovo are determined, finding two gene ratios, 6∶2 and 5∶3, to be the most prevalent among the hy reassortants analyzed, although other gene ratios also conferred hy in certain reassortant phenotype.

New technologies for influenza vaccines

The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches.

Cloning of the canine RNA polymerase I promoter and establishment of reverse genetics for influenza A and B in MDCK cells

The eight-plasmid DNA transfection system for the rescue of influenza virus from cloned influenza cDNAs was adapted such that virus can be generated directly from MDCK cells and therefore provides a tool for influenza pandemic preparedness.

Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings

Transmissibility is substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics, by analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, which makes an early assessment of transmissibility and severity.

Influenza virus titration, antigenic characterization, and serological methods for antibody detection.

While serological methods rarely yield an early diagnosis of acute influenza virus infection, well-timed, paired acute, and convalescent serum samples may establish the diagnosis of a recent influenza infection even when attempts to detect the virus are negative.

Trivalent MDCK cell culture-derived influenza vaccine Optaflu® (Novartis Vaccines)

A review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cellculture-based flu vaccines.

Rapid generation of pandemic influenza virus vaccine candidate strains using synthetic DNA

Rapid generation of pandemic influenza virus vaccine candidate strains using synthetic DNA is described in Verity et al. (2011), which aims to accelerate the generation of influenza virus vaccines using syntheticDNA.