Over the past quarter century, each occurrence of new avian and swine influenza viruses making the jump into human populations and triggering epidemics has been cause for concern that this one could be another “big one,” launching another global flu pandemic.
The World Health Organization (WHO) defines a flu pandemic as a worldwide spread of infection from a new influenza virus to which humans have little or no immunity. Pandemic designation is based on assessments of how and how fast a virus is spreading, rather than relative severity of its effects.
All of history’s great influenza pandemics stemmed from a newly-mutated virus strain making the leap from bird to mammal, examples being the Spanish flu epidemic that killed an estimated 30 million to 70 million people worldwide in 1918-’19, the Asian flu that killed than 70,000 Americans when it first appeared during the 1957-58 flu season, and the Hong Kong flu of 1997-’98 — the latter considered a relatively mild pandemic, killing about one million people globally. For context, an estimated 500,000 people die around the world annually from seasonal flu.
However, it’s impossible to predict at the outset of an influenza epidemic, such as the new H7N9 that’s been ramping up in China over the past couple of months, whether it will develop into a pandemic or its eventual global severity and effects, in the event of its developing into a pandemic, will resemble the “mild” Hong Kong flu, or become a global catastrophe.
Ominously, an April 18 article by Quartz’s Adam Pasick reported growing evidence that the H7N9 virus may have developed the ability to be transmitted between humans, especially close family members, with the Chinese government acknowledging that as a possibility for the first time, the Chinese National Health and Family Planning Commission admitting on Thursday that human-to-human transmission in the case of a Shanghai family — two brothers, at least one of whom has the virus, and their 87-year-old father, who was the first confirmed H7N9 fatality — cannot be ruled out. A husband and wife in Shanghai also both contracted H7N9. The WHO has also noted that some of the H7N9 patients have had no contact with poultry, making human-to-human transmission a potential likelihood. Pasick observes that a strain of avian flu with a high mortality rate and capable of effective human-to-human transmission, “would have the makings of a disaster film.”
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The name “influenza” derives from the Italian word for “influence,” 16th-century astronomers having deduced that the disease’s seasonal flare-ups were influenced by the stars. Today we know that the flu cycle and the appearance of constantly mutating strains of the disease is partly related to travels of migratory birds in Southeast Asia, as with all subtypes (but not all strains of all subtypes) of influenza A virus adapted to birds, which is why many are referred to as avian flu viruses.
Wild bird populations typically manifest only mild influenza symptoms, but when flocks of domesticated birds such as chickens or turkeys become infected via wild bird vectors such as bird feces, flu strains tend to develop much more deadly mutants, especially in cultures where there is close quarters interaction among fowl, pigs, and humans, often under less than optimum hygienic conditions, such as in live markets in Asian cities where a wide variety of avian species, including chickens, ducks, turkeys, pheasants and guinea fowl, as well as often pigs, are concentrated together for sale directly to the public. This provides ideal conditions for genetic mixing and spreading of flu viruses, leading to evolution of influenza virus strains adapted to multiple species. It is considered easy for humans to become infected with influenza from birds, although human to human transmission tends to require close and sustained contact, at least in the early stages of an epidemic.
However, in 2013 we do have prophylactic and therapeutic tools and agents that were not generally available in 1918, 1957, and 1967 — flu vaccines and antiviral drugs — although neither is anything close to being a “magic bullet” type solution to a potential pandemic threat. We also have more and better infrastructure and international cooperation surveillance protocols and reporting rules in place to detect, and hopefully get out in front of severe flu epidemics. DNA analysis has become quicker, and the cost of full genetic sequencing continues to decline. The U.S. reportedly has 68 million courses of antiviral drugs stockpiled along with 18 million respirators and 31 million face masks, and is investing in research to create better examples of all three. And the federal government’s Biomedical Advanced Research and Development Authority (BARDA) issues contracts with companies to develop new ways to counteract biological threats, reportedly with 130 products in development, including 45 targeting influenza.
Capacity to develop and distribute new vaccines is also greater than ever before, with BARDA having awarded contracts for three new centers, to be led by Texas A&M University in collaboration with GlaxoSmithKline (GSK), Novartis, and the Maryland firm Emergent BioSciences, to develop and manufacture medical countermeasures, including flu vaccines.
Internationally, the WHO has awarded grants to flu-vaccine manufacturers in 14 countries, four of which are currently up and running. In 2011 the WHO created a new framework for sharing flu viruses, with GlaxoSmithKline the first company to sign on. GSK Vaccines produces 30 vaccines worldwide, eleven of which are licensed by the U.S. FDA.
Late last month, the Texas A&M system and GlaxoSmithKline received U.S. Government approval to establish a new $91 million facility in Texas to develop and manufacture GSK’s next generation of influenza vaccines to counter potential global pandemics. The flu vaccines manufacturing operation will serve as the anchor of the Center for Innovation in Advanced Development and Manufacturing (CIADM) at Bryan-College Station. Texas Governor Rick Perry commented at the public announcement of the project that the Texas A&M Center, anchored by this facility, is, per an economic impact study, expected to bring more than $41 billion in expenditures to the State of Texas over the next 25 years, and will provide more than 6,800 direct and related jobs to the state. Local governments will earn a projected $339.93 million in revenue, while the state will get $849.12 million.
The Texas A&M influenza vaccines manufacturing center will provide GlaxoSmithKline with the capability to eventually manufacture influenza vaccine based on a proprietary cell-culture line, EB66. Most existing influenza vaccine is manufactured using fertilized chicken eggs. GSK’s cell-culture process will supplement the vaccine supply from eggs, and facilitate a rapid national vaccine response in the event of a pandemic. The Texas A&M-GSK venture will complement and support the company’s existing influenza vaccines operations, based in Quebec, Canada, and Dresden, Germany. GSK’s operations hub in Marietta, Pennsylvania will package, inspect and distribute influenza vaccine manufactured at the Texas A&M Center.
One of only three CIADMs to be developed in the U.S., the Texas A&M Center will be at the vanguard of U.S. pandemic-preparedness efforts, and represents unprecedented public-health collaboration among state and federal governments, academia and private industry. Once constructed and operational, the Center’s influenza manufacturing facility will be able to supply 50 million doses of pandemic influenza vaccine within four months of an outbreak. BARDA conceived the public-private formula to assure a strong biosecurity product development and manufacturing base on U.S. soil, ensuring that the nation would have rapid access to vaccines and therapeutics in the advent of influenza pandemics, or chemical, biological, radiological, and nuclear attacks.
“GSK is privileged to deepen our commitment to U.S. public health, as part of this unprecedented public-private collaboration to protect against pandemics and bio-threats,” GSK Vaccines Senior Vice President Antoon Loomans commented in a release. “In Texas A&M we have found a partner with a rich tradition of service, and with pioneering technologies that will benefit the entire pharmaceutical industry in making vaccines available and accessible to all in need.”
“We are honored to welcome GSK to Texas A&M as a key partner in the Center for Innovation,” says A&M System Chancellor John Sharp. “GSK’s dedication to public service is well-aligned with the Texas A&M tradition of serving the nation and defining its future through research and scholarship. Equally important is the cultural and philosophical match between GSK and the A&M System, as reflected by GSK’s desire to collaborate with academia and the U.S. government, and their ongoing commitment to helping address global health scourges such as pandemic influenza and malaria.”
The Texas A&M Center for Innovation is lead by Dr. Brett Giroir, Vice Chancellor for Strategic Initiatives at the Texas A&M System, and a core team of A&M experts in biotechnology, infectious diseases, facilities planning and construction, federal acquisitions/contracting, and government affairs. The university’s partnership with GSK was founded on a long, collaborative relationship between Texas A&M and the Wallonia Region of Belgium, with specific planning for this project beginning in the spring of 2010.
“GSK’s decision to partner with Texas A&M and bring their vaccine manufacturing to our state is a testament to the investments that the A&M System and the State of Texas have made in the people, infrastructure and technologies, much of which came from critical state programs such as the Emerging Technology Fund,” Giroir said in the TAMU release. “GSK brings unequaled influenza vaccine development, manufacturing, and regulatory expertise to our Center. Equally important, GSK brings its cell based influenza vaccine development program, which we have assessed to be the most promising near term influenza vaccine technology to improve upon current egg based vaccines.”
The Texas A&M Center for Innovation represents the largest commitment of a global biopharmaceutical company to partner within Texas, and is expected to be an important catalyst to future growth of this industry in the State.
Nevertheless, providing timely access to effective flu vaccines for upwards of two billion people in the event of a pandemic remains a daunting challenge,
Flu vaccines can protect people against some viruses, especially common ones already widely disseminated, but typically are less effective against new and novel strains, and the composition of a particular flu virus “cocktail” is dependent on how accurately its formulators guess the identities of the next wave of epidemic-causing flu strains.
Consequently, time is of the essence with respect to developing a new vaccine as a foil to a potential pandemic caused by H7N9, which has now spread beyond the region of Eastern China where it was first detected, and all known human cases had manifested until this month. Vaccine availability often comes too late for the bulk of a particular disease strain’s victims, as was the case with vaccines for the H1N1 epidemic of 2009-’10 – a strain that proved contagious but capable of only limited human-to-human transmission and not especially deadly, which was fortunate because H1N1 vaccines took months to deploy, both due to unavoidably necessary development time, and also bureaucratic holdups in distribution.
There are also factors in 2013 that didn’t apply in 1918, 1957, and 1967 that exacerbate pandemic potential, such as a much higher global population, the proliferation of cheap and frequent air travel, and the globalization of food supply channels.
In 2012, GlaxoSmithKline provided more than 20 million flu shots for the U.S. market and recently became the first major U.S. vaccines provider to gain FDA-approval for a broader-protection, four-strain (quadrivalent) influenza vaccine shot that will be available in time for the 2013-14 flu season. Hopefully, it will prove effective against H7N9, should that become an emergent priority.