Annual Flu Vaccine in Children Builds Strong Immune Response

Kate Johnson

February 07, 2022

Children who received seasonal influenza vaccines several years in a row developed robust titers of broadly neutralizing antibodies (bNAbs), according to a new study from McMaster University in Hamilton, Ontario, Canada.

"The benefit of broadly neutralizing antibodies is that they are not strain specific and can therefore provide protection against diverse strains or subtypes of influenza virus," a feature that is important in the quest for a universal influenza vaccine, said senior author Matthew Miller, PhD, associate professor at the university's Michael G. DeGroote Institute for Infectious Diseases Research.

"The most important message of the paper is that getting seasonal influenza vaccines year after year appears to be a very good thing for young children," he said. Not only do annual vaccines generate strain-specific immunity in children, "they also generate strong bNAb responses that could protect them in the event of a pandemic."

In adults, universal flu vaccine development has advanced to a clinical trial testing a vaccine designed to elicit bNAbs, but much less has been done in children, Miller said. "Our study set out to advance our understanding of how universal vaccines need to be tailored for pediatric populations." The findings were reported in Cell Reports Medicine.

The researchers evaluated immune responses in serum samples from participants of a cluster-randomized control trial. The original trial compared the community-level protection mediated by either inactivated virus (IIV) or live attenuated virus (LAIV) vaccination in children.

Using samples from 68 participants (37 IIV vaccinees and 31 controls; median age, 9 years), the team examined the serologic induction of bNABs for each of the three vaccination seasons (2008/09 to 2010/11). The study included another 72 participants to compare both serologic and muscosal bNABs induction by vaccine formulation (35 who received IIV and 37 who received LAIV).

To examine serologic bNAB induction, researchers compared prevaccination microneutralization (MNT) titers to titers after three influenza seasons. They found higher titers in vaccinated participants compared to controls. Specifically, 43% of vaccinees had at least a fourfold increase of MNT, compared with 13% of controls.

The finding demonstrates that repeated seasonal IIV vaccination induces durable bNAb responses in children, the authors note. They also note that the magnitude of bNAb response was inversely correlated with age.

The researchers also compared serologic vaccine-induced bNAb responses in those vaccinated with IIV vs LAIV, and they found no significant differences.

In addition to serologic antibody response, the study also examined mucosal response. Vaccination increased mucosal bNAb titers similarly between vaccine types, the authors report.

The data suggest that both IIV and LAIV vaccine formulations "might be equally suitable" for delivery of pediatric universal influenza vaccines and that "the threshold for inducing bNAbs in children may be lower than in adults, for whom seasonal vaccines do a poor job at boosting bNAbs," the authors wrote.

"A lot of prior work has been done showing that, in adults, seasonal vaccines elicit narrow, primarily strain-specific responses," Miller told Medscape. "This is due in part to their immune systems having been extensively 'imprinted' by prior exposures to the virus — due to earlier infections and/or vaccinations. We have learned how to 'trick' the adult immune system into generating bNAbs by exposing them to very unusual influenza viruses — typically, viruses to which humans are not normally exposed.

"In contrast, what our study shows is that the immune system of children produces bNAbs much more readily after seasonal vaccination — probably because they have not been as extensively imprinted by prior exposures to flu," Miller said. "But, as the children age and their immune system becomes progressively more 'imprinted' and adult-like, their capacity to produce bNAbs in response to seasonal vaccines progressively diminishes."

The observation that children have a greater propensity than adults to generate bNAbs is an important one, said Jenna Guthmiller, PhD, postdoctoral fellow at the University of Chicago and incoming assistant professor in the Department of Immunology and Microbiology at the University of Colorado Anschutz Medical Campus.

"To my knowledge, this is the first paper to get a good grasp on this concept in relation to vaccination and children," Guthmiller told Medscape. "It's largely thought that adults have more bNAbs, as it was thought that they take time [to develop through] multiple exposures. This study suggests it only takes a few exposures. These data are exciting from a clinical perspective in that they suggest that children have the ability to generate broad and protective immunity against influenza viruses. The authors also identified that broadly neutralizing antibody responses tended to decline with age, suggesting new vaccines are needed to specifically maintain high levels of broadly neutralizing antibodies in childhood and into adulthood."

The study was supported, in part, by a Canadian Institutes of Health Research (CIHR) Project Grant, a CIHR New Investigator Award, an Ontario Early Researcher Award, a Canada Research Chair in Viral Pandemics, an Ontario Graduate Scholarship, and an M. G. DeGroote Postdoctoral Fellowship. The authors and Guthmiller Guthmiller have disclosed no relevant financial relationships.

Cell Rep Med. Published online February 3, 2022. Full text

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.

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