At 36 percent overall effectiveness in preventing the flu in the U.S., this season's influenza vaccine is not playing to much applause, and it's leaving policy makers wanting so much more – like a long-lasting universal vaccine.

At 36 percent overall effectiveness in preventing the flu in the U.S., this season's influenza vaccine is not playing to much applause, and it's leaving policy makers wanting so much more – like a long-lasting universal vaccine.

While the NIH and Biomedical Advanced Research and Development Authority (BARDA) are working toward that vaccine, no one is expecting a premiere anytime soon. Until that day arrives, "I hope we continue to take steps, even if they're nanoparticle steps, to get to that conclusion," Rep. Gregg Harper (R-Miss.), chairman of the House Energy and Commerce Subcommittee on Oversight and Investigations, said at a subcommittee hearing Thursday.

During the hearing, government health experts coached lawmakers on what some of those steps should be, while advising them on the market challenges in upping the performance of vaccines through new technologies.

In pushing for greater use of new vaccine technologies, BARDA Director Rick Bright and Anthony Fauci, director of the NIH's National Institute of Allergy and Infectious Diseases, bemoaned the continuing reliance on the egg-based vaccines of yesteryear. Although the FDA approved Seqirus' Flucelvax as the first cell-based vaccine in 2012 and Flublok, a recombinant vaccine developed by Protein Sciences Corp. (now part of Sanofi SA), a year later, most of the flu vaccines in the U.S. still use the egg technology developed 70 years ago.

While the cell-based and recombinant technologies potentially offer greater efficacy, more quickly, and with the flexibility to rapidly shift to keep pace with changes in the virus, only 18 percent of the vaccines available this season were cell-based and 3 percent were recombinant, Bright said. He attributed the underutilization of the newer technologies on marketplace competition and limited domestic production capacity.

Fauci pointed out that whenever there's a time-honored, proven technology, there's an inertia to switching to a new technology. But when it comes to vaccines, "we've got to go there," he said. "We can't stay stuck in the technology."

That may take a policy rethink of how vaccines compete and incentives to encourage vaccine makers to invest in new technologies. For instance, the current inability to differentiate cell-based and recombinant technologies in the marketplace offers little reason for a company to update its manufacturing, Bright said.

FDA Commissioner Scott Gottlieb said existing vaccine makers would have to make an enormous investment to change from egg-based manufacturing to a newer technology. But the rise of continuous manufacturing could encourage that switch, he added. It's something the FDA plans to explore, if it gets the funding in the fiscal 2019 budget.

Bright noted that it's not enough for a company to get a new vaccine licensed. It also must have the vaccine available in sufficient quantity – and then hope it is used that season. Otherwise, the company would be left with inventory it can't use and be forced off the stage.

Meanwhile, the demand for the flu vaccine isn't as great as it could, or should, be. For the past several years, about 48 percent of Americans have gotten the flu vaccine. That could be due to urban myths about the vaccine and the efficacy data.

No, the flu vaccine cannot give anyone influenza, Anne Schuchat, acting director for the CDC, responded to a lawmaker's question. Too often, people mistake symptoms from other bugs with the flu. And the overall effectiveness of a vaccine doesn't tell the entire story, as it doesn't reflect how the vaccine can lessen the severity of the symptoms. One of the challenges the CDC faces is how to tell that story to the public and doctors.

Poor performance

In all fairness, this season's vaccine isn't the worst performance in recent years. That dishonor would have to go to the 2014-2015 vaccine, which had a 19 percent overall effectiveness due to a mismatch of the strains chosen for the vaccine and the wild strains that actually made their way around the country.

Mismatches can occur when unexpected strains put in an appearance or the predicted strains evolve so they no longer match the ones selected early in the year for the vaccine. (Using a cell-based or recombinant technology would shorten the window between strain selection and manufacture, which could lead to a better match.)

The most difficult challenge for flu vaccines has been taking on H3N2 influenza A viruses that dominated much of this year's flu season. Thus, H3N2 tends to result in "more cases, more visits to the doctor, more hospitalizations and more deaths, especially among older people," Schuchat said.

Preliminary data for the 2017-2018 flu season showcase the difficulty with H3N2. While this year's vaccine had an overall effectiveness of 36 percent, its effectiveness against H3N2 viruses for all ages was 25 percent, compared with 67 percent against influenza A (H1N1) viruses and 42 percent against influenza B viruses. Broken down by age group, the vaccine's H3N2 efficacy was only 17 percent for people 65 and older, while it was 51 percent in children 6 months to 8 years of age. (See BioWorld, March 2, 2018.)

Theories abound about why the vaccine is underperforming against H3N2, Schuchat said. The CDC, which characterizes thousands of flu viruses throughout the year, hasn't noticed a significant antigenic drift in the H3N2 virus that's circulating this season, but it did see differences between the viruses prepared for manufacturing the egg-based vaccine and the wild-type H3N2 viruses. The egg-adapted changes could be one of several possible contributors to the vaccine's lackluster performance this year, Schuchat said.

To help provide some of the answers, the FDA is using Medicare data to compare the efficacy of the egg-based vaccine with the newer cell-based vaccines. The agency also is exploring efficacy differences with standard-dose vs. high-dose flu vaccines and an adjuvanted vaccine, Gottlieb testified.