H7N9

Greffex  H7N9 (HPAI) VaccineThe recently emerging H7N9 highly pathological “avian” influenza (HPAI) was characterized by Keiji Fukuda assistant director-general for health security of the World Health Organization (WHO), as an “unusually dangerous virus for humans.” In the last month, bird carriers have infected more than 100 patients, caused more than 20 deaths, and the disease has moved beyond the environs of Shanghai to Taiwan. Although only sporadic human-to-human transmission has so far been seen, only a few mutations within the H7N9 genome may be necessary to enhance its infectivity thus creating a fast moving and dangerous pandemic. The emergence of H7N9 represents another example that challenges the current influenza vaccine paradigm that is built on virus identification in late winter, vaccine production in spring and summer, followed by a vaccination campaign in fall.

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What is needed is a novel vaccine platform that responds to a newly emerging influenza within weeks rather than months whenever and wherever it occurs. It has to combine speed with potency and versatility. Greffex’s GREVAX platform meets these mandates. Its design builds on the immunogenicity of an adenoviral vector; deleted of all adenoviral antigens it focuses the immune response to the H7N9 influenza antigens; its modular components combine flexibility of composition with speed of production. Indeed, Greffex is presenting today, about one month after the identification of the H7N9 influenza, a completed GREVAX H7N9 vaccine construct. This H7N9 vaccine candidate is ready for production and testing.

Background

Influenza, commonly called flu, is a seasonal infectious disease of the respiratory tract. The illness begins 1 to 4 days after infection with constitutional and respiratory symptoms, including fever, myalgia, headache, general malaise, coughs, sore throat and rhinitis. Generally it resolves within 1 week. Yet the disease can be complicated by primary viral pneumonia exacerbating underlying cardiac conditions, and by bacterial superinfections, such as bacterial pneumonia and otitis media. Both primary and secondary illnesses can result in death. Each year, the global burden of the “conventional” influenza is believed to be 3 to 5 million cases of severe illness and 300,000 to 500,000 deaths worldwide (36,000 in the US).

Besides the more benign seasonal outbreaks, highly virulent recombinants associated with high levels of morbidity, appear every 10 to 50 years. The most noteworthy influenza pandemic (H1N1) occurred in 1918 when more than 20 million perished worldwide. Another outbreak was seen in 2009, when a novel H1N1 (“swine”) influenza began to spread. It contained a unique combination of gene segments found in American and Eurasian swine lineage. Luckily it was of limited pathogenicity.

Avian Influenza (H7N9 virus) does not represent the first threat with a highly pathological “avian” influenza (HPAI). Prior to H7N9, the H5N1 strain (A/Vietnam/1203/2004) originating in Southeast Asia was identified. It again demonstrated the threat that influenza viruses pose to humanity. Since 2004, it has moved throughout the world, infecting both domestic poultry and migratory birds, but also “spilling over” into the human population. Several hundreds have been infected by H5N1, often the young, of whom almost half succumbed to a severe disease (CDC, WHO).

H7N9 Avian Influenza, a potentially even more dangerous HPAI surfaced in Shanghai in late March of this year. Three residents around Shanghai, China, were hospitalized suffering from a severe and fatal acute respiratory distress syndrome (ARDS). Upon investigation, a novel reassortant avian influenza virus strain was identified as culprit. Three versions of H7N9 influenza virus (A/Shanghai/1/2013; A/Shanghai/2/2013; A/Anhui/1/2013) were isolated. Their genes exhibited minor variations and were all of avian origin. Subsequently, more than 100 additional human cases H7N9 influenza have been identified. The overall lethality of this HPAI has been around 20%. The infection has spread beyond China. A Taiwanese businessman, who had earlier traveled to Eastern China, was recently diagnosed with a severe form of H7N9.

“This is an unusually dangerous virus for humans,” said Keiji Fukuda of the WHO. Indeed, aspects of the H7N9 avian influenza outbreak make it difficult to control and thus dangerous, more so than even the H5N1 virus. Infections in birds are silent, and some human cases are asymptomatic or present as only a mild form. The human population is not protected against the disease by pre-existing immunity. Finally, some evidence suggests that person-to-person transmissions is possible. However, if the virus further evolves and moves into sustained human-to-human transmission, it has indeed the potential to wreak havoc throughout the world. An initial infection of 10 individuals in the US may spread to more than 90% of US citizens within 90 days. As it has been demonstrated that the infectivity of an HPAI could increase with only a few genetic modifications, it has become mandatory to prepare the world for such a potentially devastating scenario, if not for H7N9, then for another HPAI that will certainly develop in the future.

The Need

The WHO considers the H7N9 outbreak as “one the most lethal influenza viruses” that have been seen. A stable adaptation of H7N9 to humans will make its tracking and its control in densely populated communities impossible. Treatment with some antivirals may be efficient if provided early after infection. Nevertheless, efficient vaccination remains the only means to halt the spread of the disease and thus to protect humanity. Indeed, the US Centers for Disease Control and Prevention (CDC) have initiated the production of a “standard” H7N9 influenza vaccine that will be completed within 7 months. If the H7N9 continues to spread and moves to sustained human-to-human transmission, a lead-time of 7 months for the production of a protective vaccine will be too long. Therefore, a novel approach will have to be employed that delivers potent vaccines within weeks rather than months. Besides speed, this system has to be versatile to accommodate not only H7N9, but also other dangerous influenza strains that will hit in the future.  

The Greffex Solution

Greffex’s GREVAX™ vaccine platform has been purpose-built with a high level of plasticity to deliver protection against emerging infectious threats. It incorporates the following features: potency, versatility and speed.

Potency: GREVAX vaccines exploit the well-established potent immunogenicity of adenovirus-based engineered vaccines. They focus immune responses to vaccine antigens as they are fully deleted of adenoviral genes and devoid of helper viruses.

Versatility: GREVAX modules allow a flexible plug-and-play design of vaccines for emerging infectious disease, including but no limited to the H7N9 HPAI.

Speed: The GREVAX vaccine platform was created to develop vaccines within about one month. It incorporates a fast vector construction time with a standardized vaccine production scheme. The genetic information for the H7N9 influenza strain was uploaded in early April 2013. Greffex was able to deliver the respective GREVAX H7N9 vaccine candidate by May 1, 2013.

Besides an H7N9 vaccine, Greffex has already used the GREVAX platform to develop a host of different vaccines, including different influenza vaccines, as well as Anthrax, Dengue and Ebola vaccines.