Study suggests adjuvanted flu vaccine benefit for children under age 2

A large study in children ages 6 months through 5 years that compared an adjuvanted flu shot with the inactivated injectable version found that, overall, both offered similar protection against lab-confirmed flu, but the adjuvanted vaccine was significantly more effective in the youngest age-group. An international group, which included researchers from Seqirus, the maker of the adjuvanted vaccine, published its findings in The Lancet Respiratory Medicine.

The 2-year study took place at 146 sites in 9 countries during 2013-14 and 2014-15 flu seasons, enrolling 10,644 participants. In the randomized, controlled, observer-blinded study, of 10,612 children who were vaccinated, 5,338 received the inactivated injectable quadrivalent vaccine that contained the MF59 oil-in-water adjuvant and 5,274 got either the trivalent or quadrivalent inactivated influenza vaccine. Most of the flu infections during the trial occurred during the 2014-15 season, when H3N2 was the predominant strain and was a poor match with the vaccine strain.

Children younger than 3 received one or two 0.25-milliliter (mL) doses, depending on previous vaccination status, and those ages 3 to 5 got one or two 0.5-mL doses, also depending on earlier vaccination. Kids who received a second dose were vaccinated 29 days after the first.

Relative vaccine efficacy didn't vary for the two vaccines in the overall study population, but in kids ages 6 through 23 months—the population most vulnerable to severe flu outcomes—efficacy was significantly greater for the adjuvanted vaccine. In the wider age-group, the adjuvanted vaccine showed superior immunogenicity. Safety profiles were similar, but adverse events were higher in the adjuvanted vaccine group, with most mild to moderate and short.

The researchers noted that despite the disadvantage of the mismatch between the circulating and vaccine strains, the adjuvanted vaccine was still more effective against flu in the youngest group.

In a related commentary in the same issue, Kathleen Neuzil, MD, PhD, and research assistant Elizabeth Rotrosen, both with the Center for Vaccine Development at the University of Maryland School of Medicine, wrote that the Northern Hemisphere's current season is a reminder of how vulnerable young children are to flu complications. They said more effective flu vaccines are needed for kids, but it's expensive and difficult to do comparative studies to help weigh new vaccine and guide policy.

They said the new study was well conducted and sufficiently powered. They noted that the authors used a half-dose of nonadjuvanted vaccine in the youngest group, though many countries recommend a full dose for all age-groups. That most of the study's findings were driven by the 2014-15 season shows how challenging flu studies can be, given a host of variables that also include different circulating strains and flu season timing, they wrote.
Apr 6 Lancet Respir Med abstract
Apr 6 Lancet Respir Med commentary

Researchers discover potential for flu vaccines that target neuraminidase

Though current flu vaccines target the hemagglutinin (HA) surface protein on the virus, new vaccines that target the neuraminidase (NA) protein might provide strong cross-protection against a range of strains, a research team supported by the National Institute of Allergy and Infectious Diseases (NIAID) reported recently in Cell.

Several efforts are under way to develop better flu vaccines, and the scientists that reported the new findings are part of NIAID's Center of Excellence for Influenza Research and Surveillance (CEIRS). First, they looked at blood samples from people vaccinated against flu and those who had been diagnosed as having 2009 H1N1 or H3N2 influenza. The team found that flu vaccines rarely prompt NA-reactive antibodies, but natural infection induces them at least as often as HA-reactive antibodies. Next, they conducted more lab tests that showed the NA-reactive antibodies produced during natural infection were broadly reactive, with the potential to protect against diverse flu strains.

To test the theory in mice, they isolated NA-reactive monoclonal antibodies from people who had been sick with H3N2 or H1N1, administering 13 N2-reactive antibodies prior to experimental infection with a different H3N2 virus strain. Of the 13 antibodies, 11 partially or fully protected the mice. Of 8 N1-reactive antibodies that they gave another group of mice, 4 completely protected the animals after a challenge with a similar H1N1 virus or an H5N1-like virus.

The researchers concluded that flu vaccines could be enhanced to target NA for broader protection against diverse flu strains.

In a press release, the NIAID said it is supporting further research to characterize NA response in infected and vaccinated people and to determine the mechanism of action of NA protection. It also added that it supports a CEIRS working group to identify knowledge gaps of NA and set NA research priorities for improved flu vaccines. "These efforts contribute to NIAID's larger plan to develop a universal influenza vaccine—a vaccine that can durably protect all age groups against multiple influenza virus strains," it said.
Apr 5 Cell abstract
Apr 6 NIAID press release