Members of the FDA's vaccines advisory committee met Thursday to tackle what they recognize as their most challenging task – recommending influenza strains to be included in vaccines for the next flu season.

Despite all the detailed data presented at the meeting about this season's flu strains, "you're still sitting with a crystal ball," Pamela McInnes, deputy director of the NIH's National Center for Advancing Translational Sciences, said as she and the other members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) prepared to vote on the strains for the 2018-2019 flu season.

She has spent sleepless nights after previous selection meetings, McInnes said, as she hoped she and the other members of the committee had made the right decision.

After hours of poring over flu distribution maps and timelines, along with the genetic characteristics of the various clades and subclades of the influenza strains currently circulating, the committee voted unanimously to advise the FDA to go with the strains the World Health Organization recommended for vaccines in the Northern Hemisphere.

Meanwhile, U.S. lawmakers and federal agencies are pursuing advances that eventually could make such adcom meetings obsolete. The NIH unveiled a strategic plan Wednesday focusing on research areas essential to creating a safe and effective universal influenza vaccine. Specifically, it calls for research to:

• improve the understanding of the transmission, natural history and pathogenesis of influenza infection;

• precisely characterize how protective influenza immunity occurs and how to tailor vaccination responses to achieve it;

• support the rational design of universal influenza vaccines, including designing new immunogens and adjuvants to boost immunity and extend the duration of protection.

Congress is already looking to provide funding for the research. The Flu Vaccine Act, which was introduced in the Senate a few weeks ago, was introduced in the House this week. In introducing the bill, Rep. Rosa DeLauro (D-Conn.) said the development of a universal vaccine would spare health officials the challenge of predicting what flu strains a seasonal vaccine will have to fight. More importantly, it would save "lives by taking the guesswork out of the equation," she added.

Hefty toll

The toll of the current flu season punctuates the need for a universal vaccine. Sen. Edward Markey (D-Mass.), who is sponsoring the Flu Vaccine Act in the Senate, said that as of mid-February, 63 children had died from the flu this season and one in 10 Americans who died the week ending Jan. 20 died from the flu or pneumonia. Part of the problem was the efficacy of this season's vaccine, which varied widely by age group.

For example, the effectiveness of the vaccine against H3N2, an influenza A strain, was 25 percent overall, but 51 percent in children 6 months to 8 years old and 17 percent for people 65 years and older. Its effectiveness against H3N2 was even lower for older children and younger adults. However, the vaccines were more effective against other strains, with the data showing overall vaccine effectiveness for H1N1 and influenza B was 67 percent and 42 percent, respectively, according to a statement FDA Commissioner Scott Gottlieb released this week.

The efficacy issues, specifically with the H3N2 strain, were a concern at Thursday's adcom, and several committee members stressed the need for more research. Noting that H3N2 appears to drift when the vaccine is manufactured in eggs, Paul Offit, a professor of vaccinology at the Perelman School of Medicine at the University of Pennsylvania, asked what the FDA is doing to move toward cell-based technology for vaccines.

Marion Gruber, director of the FDA's Office of Vaccines Research and Review, responded that there's been a lot of discussion on the subject. The problem is that cell-based vaccine technologies are young, so there's not as much data on them as there is for egg-based vaccines.

Jacqueline Katz, director of the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, said, "What we really need is systematic vaccine trials where we get good serologic information" that can answer questions like why a vaccine failed.

Leonard Friedland, the industry representative on the committee and vice president of scientific affairs and public health, vaccines at Glaxosmithkline plc, agreed on the need for more research into new vaccine technologies, noting that many of the vaccines being used today use technology developed in the 1940s. However, he reminded his colleagues that the current vaccines – 90 percent of which are egg-based – are working for a lot of people.

That's a fact that often gets lost in public discussions, which can undermine confidence in vaccines by focusing on what went wrong rather than what worked, several committee members acknowledged.

A case in point is the letter Markey and seven other senators wrote to Health and Human Services Secretary Alex Azar last month requesting details on how the department plans to address the problems of developing what they called "a less than optimal, stop-gap flu vaccine every year."

A House subcommittee announced Thursday that it will hold a hearing March 8 to examine how public health agencies prepare and respond to seasonal flu and why this year's flu vaccine has reduced effectiveness against H3N2.

The FDA is already looking into that question. Gottlieb said Monday that FDA scientists are working with colleagues at the Centers for Medicare & Medicaid Services to use a database that includes details of the flu vaccines administered to 4 million individuals, along with whether they were hospitalized for influenza or treated with antiviral medications for influenza-like illness. The FDA also is working with other federal agencies to examine various factors "that might be contributing to the less than optimal overall protection provided by this season's vaccines against influenza," Gottlieb said.

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