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High-dose Flu Shot Protects Better Against Virus, Study Finds

Good news for people who received a high-dose recombinant influenza vaccine this year. The vaccine offers more protection against flu than an egg-based standard-dose vaccine for older adults aged 50 and 64 years, findings published on Dec. 14 in The New England Journal of Medicine found. 

A team from Kaiser Permanente Northern California gave flu shots to more than 1.6 million patients ages 18 to 64 years. A total of 632,962 people received either the high-dose quadrivalent (four-strain) flu vaccine, while 997,366 people got one of two standard-dose vaccines. They were inoculated in the 2018-19 and 2019-20 respiratory virus seasons. The team compared how effective the shots were against infection and hospitalization.

Of the 675,252 older adults who were between the ages of  50 to 64 years, 41.4% received the recombinant vaccine, and 58.6% were given a standard-dose vaccine.

Then the team looked at flu tests. Of 16,340 tests performed, 23.4% were positive for the flu; 38.8% of cases were in people aged 50 to 64 years and 16.7% of them were hospitalized.

Among the older adults, 559 of 1,386 people in the recombinant group developed the flu compared to 925 out of 2,435 people in the standard-dose group. That means there's a relative vaccine effectiveness of 15.3%.

The four-strain flu shot made by Sanofi is made without chicken eggs. This means it has a recombinant hemagglutinin protein that is genetically identical to the one in the strain of the flu virus — a perfect match.

"In traditional quadrivalent standard-dose inactivated influenza vaccines (SD-IIV4), chicken eggs are used to manufacture the influenza virus," the authors wrote. "Mutations in the hemagglutinin protein during egg-based manufacturing can result in mismatch between the selected strain and the vaccine strain."

If standard-dose vaccines were already preventing most cases of influenza and breakthrough cases were uncommon, preventing 15% of breakthrough cases wouldn't be much of a public health perk, according to the researchers. 

"However, since standard-dose vaccines prevent at most 40 to 60% of influenza cases annually, reducing the incidence of breakthrough influenza by 15% would provide a substantial public health benefit, especially during more severe influenza seasons," they said.

High-Dose Recombinant Flu Vax Offers More Protection For Adults 50 To 64

A high-dose recombinant influenza vaccine (Flublok Quadrivalent) was more protective than an egg-based standard-dose influenza vaccine in adults, according to results of a cluster-randomized, observational study.

Among adults ages 50 to 64, the high-dose vaccine was 15.3% more effective in preventing influenza than the standard-dose vaccine (95% CI 5.9-23.8, P=0.002) and 15.7% more effective against influenza A (95% CI 6.0-24.5, P=0.002), reported Nicola Klein, MD, PhD, from the Kaiser Permanente Vaccine Study Center in Oakland, California, and colleagues in the New England Journal of Medicine.

Although the relative benefit of the high-dose vaccine appears to be modest, "reducing breakthrough influenza cases by 15% would provide a substantial public health benefit, especially during more severe influenza seasons," Klein told MedPage Today in an email.

Georges Benjamin, MD, executive director of the American Public Health Association in Washington, D.C., agreed. "The high-dose vaccine increased protection by about 15% overall," he told MedPage Today in an interview. "When you think about the fact that we don't usually get more than 40% to 50%, maybe 60% efficacy in a good year to begin with, that's a nice boost. The study authors convinced me, that for this age range, it does provide better protection than the standard dose," he said.

Researchers did not find that the recombinant vaccine was significantly more protective than the standard-dose vaccine against influenza-related hospitalization. However, "a post hoc analysis combining hospitalization for PCR-confirmed influenza and hospitalization for community-acquired pneumonia yielded a relative vaccine effectiveness of 19.7% (95% CI 2.8-33.7)," the authors wrote.

The Advisory Committee on Immunization Practices (ACIP) currently recommends high-dose influenza vaccines for adults ages 65 and older. However, for people younger than 65, ACIP does not preferentially recommend any age-appropriate influenza vaccine over another. Recommended options for this age group include inactivated influenza vaccine, recombinant influenza vaccine, or live attenuated influenza vaccine.

The high-dose recombinant influenza vaccine evaluated in this trial is FDA-approved for adults 18 and older, and is three times the dose of standard-dose influenza vaccines.

Participants included all members of a large U.S.-based integrated healthcare delivery system over seven geographic regions. The study population included 1,630,328 people from the ages of 18 and 64 who were vaccinated for influenza in the healthcare system -- 632,962 received the high-dose recombinant vaccine and 997,366 received the standard-dose vaccine.

Although the study was observational, it had a unique cluster-randomized design "intended to emulate a randomized trial," the authors wrote. Facilities in each region were assigned to Block A or Block B to even out differences in facility size. To achieve balance between the two vaccine groups, facilities alternated on a weekly basis between administering the high-dose recombinant vaccine and the standard dose vaccine. Patients were unaware of which vaccine they received.

During the study period of the 2018-2019 and 2019-2020 influenza seasons, 1,386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2,435 cases in the standard-dose group. Among those who were ages 50 to 64, 559 participants (2 cases per 1000) tested positive for influenza in the recombinant-vaccine group and 925 participants (2.34 cases per 1000) tested positive in the standard-dose group.

The study data were limited to two influenza seasons and relative vaccine effectiveness may vary across seasons, the researchers acknowledged. In addition, participants included in the study might not be representative of other U.S. Populations.

Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.

Disclosures

The study was funded by Sanofi.

Klein has received grants from GlaxoSmith Kline, Merck, Pfizer, and Sanofi Pasteur.

Co-authors reported no relevant disclosures.

Benjamin also reported no relevant disclosures.

Primary Source

New England Journal of Medicine

Source Reference: Hsiao A, et al "Recombinant or standard-dose influenza vaccine in adults under 65 years of age" N Eng J Med 2023; DOI: 10.1056/NEJMoa2302099.

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High Dose Flu Shots Mean New Choices

HOUSTON Betty Sterba is getting the super flu shot. She'd never heard of it until this week when her doctor told her to take it.

"He said he thought it was a good idea," she said. "It's for people like me."

What is a high dose flu shot?

Kelsey-Seybold Immunization Specialist Dr. Melanie Mouzoon said, "High dose flu vaccine -- it's the same vaccine as the usual flu vaccine but it's four times as concentrated."

It's the first high dose flu vaccine and it's only for seniors, because they're the ones who most often die from the flu.

Dr. Herbert DuPont with the UT School of Public Health said, "We don't respond to vaccines as well as we get older because of the deterioration of our immune system."

Are the side effects super too?

"There's a little more soreness, a little more swelling, even some more muscle aches and pains that occur, but that means it's working," explained Dr. DuPont.

Bob Brecht chose the high dose flu shot.

"I thought, well, it's worth doing that because I want every edge that I can get," Brecht said. "I can't afford to be sick. Plus I love my grandkids want to be around them, plus we all know that kids carry a lot of things."

So it's basically a choice for seniors. But what if people under 65 want the super flu shot? Dr. DuPont says they don't need it. But there are some questions about it.

He said, "I think it's a terrific idea. The only thing missing is the science. We have to prove that it helps."

They don't know if the stronger vaccine actually prevents more cases of flu. This is the first year -- a kind of test run. The CDC is waiting to see who gets sick on the regular flu shot, and who gets sick on the super flu shot. The super flu shot does cost about $50 more, although Medicare usually pays for it.

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