Preventing – and Planning for – the Next Influenza Pandemic

SAN DIEGO, CA— Influenza surveillance and response remains an ongoing, and changing, challenge–and pandemic preparedness goes well beyond stockpiling vaccines, noted speakers at IDWeek 2015’s closing plenary session.

Work toward a “universal” influenza vaccine that would afford broad protection against multiple strains was spotlighted as one particularly hopeful – albeit preclinical – area of research, summarized by Adolfo Garcia-Sastre, PhD, of the Mount Sinai School of Medicine in New York, New York. One approach to developing a universal vaccine is to mix and match viral heads and stems from different strains to produce “chimeric” vaccines. Testing chimeric vaccines in lab animals has yielded promising protection against infections under experimental conditions.

But while Dr. Garcia-Sastre’s team is pioneering work toward better vaccines, they have also gleaned important lessons by looking to the past: the 1918 global “Spanish Flu” pandemic. Using a pathological specimen from 1918, they recreated the 1918 flu under biocontainment, and to show that mice infected with the strain lost weight and died within 5 days.

But when the researchers looked at the genetic underpinnings of the 1918 strain’s lethality, they were surprised to find not one genetic smoking gun, but several. “No single gene drove the virulence in humans” of the 1918 strain, Dr. Adolfo Garcia-Sastre said. It was instead a case of “multi-virulence, involving at least 14 genes.”

That genetic “perfect storm” makes it “very difficult to predict” when the next highly-lethal pandemic strain is likely to emerge, he noted.

To illustrate the difficulty of stemming the spread of an aggressive strain in the modern era of global transportation, Dr. Garcia-Sastre pointed to the 1957 pandemic, which started in February 1957 in Southeast Asia and had spread globally by that summer.

“Right now, the virus would spread even more quickly,” he said.

Confronting that kind of pandemic is not a challenge only because of an increasingly interconnected world, but also because of the time it takes to roll out new vaccines, he noted. “It takes time to develop a vaccine when an epidemic strain is detected,” he said.

That might become even more important, given that the seasonal epidemiology of influenza appears to be changing.

Normally, the North American influenza seasons’ infections typically peak in February or March. “Normally, that’s what we’ve seen over time,” said Daniel Jernigan, MD, MPH, of the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. “But if you look at 2013, 2014, 2015, the seasons have all been starting earlier—and it’s not just with the H3N2s that have [antigenically] drifted.”

Recombinant influenza vaccines, point-of-care diagnostic tests, and the coming next-generation portable ventilators all promise to help save lives when the next pandemic hits, but hastening vaccine development and production and moving from a “stockpile” mentality to a “response mode” state of mind, are equally important, agreed Nicole Lurie, MD, MSPH, Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services in Washington, DC.

“Vaccines come too late,” she said. For example, during the 2009 season, the vaccine worked similarly to previous years’ vaccines, but it took so long to develop and manufacture that its impact on infection rates, was muted.

H7N9 has emerged as “a real concern,” noted Lurie. The CDC’s Influenza Risk Assessment for North American strains puts H7N9 at the top of the list – ahead of H5N1, H3N2, and the emerging H5NX strains – in terms of risk of emergence and magnitude of impact if it does emerge as a pandemic strain.

“H7N9 is coming from an animal reservoir and affects some humans but seems to propagate badly from human to human,” Dr. Adolfo Garcia-Sastre said. “The concern is if any of these viruses can start to propagate in humans.”

Preventing or mitigating the next pandemic ultimately requires developing better vaccines and distributing them in a more timely fashion, Dr. Garcia-Sastre agreed.

Early detection, faster vaccine development and manufacture, and data sharing are all key to effective pandemic responses, Dr. Lurie said. HHS is updating the federal government’s pandemic influenza response plan to address changes in social media, electronic medical records, and mobile device apps, she noted, citing recent efforts by CVS Pharmacies to alert patients in South Carolina to refill their prescriptions prior to flooding, and Kaiser’s electronic medical records-driven alerts to asthma patients about hazards from approaching wildfire smoke.

“Clinical issues are incompletely understood at onset” of a pandemic, she noted, and communication is vitally important. The role of IV fluids in saving the lives of Ebola-infected patients wasn’t well recognized when the most recent outbreak began, for example. And the insight that H1N1-infected children are more likely to die from nosocomial MRSA infections than influenza infection, was delayed by slow university institutional review board approvals of information sharing with the government, she added.

Budgetary challenges mean that many surveillance partners around the world take several months to get samples to the lab for analysis, potentially slowing detection of an emerging pandemic strain, Dr. Lurie said.