MF59-adjuvanted flu vaccine improves immune response in children
SAN FRANCISCO — Young children who were revaccinated with an MF59-adjuvanted, quadrivalent influenza vaccine, or aQIV, continued to show enhanced immunogenicity against strains that were contained in the vaccine and even those that were not, researchers reported at IDWeek.
“We know that young children bear a considerable burden of illness from influenza, and that’s because of their immature or naive response to standard vaccines, including standard influenza vaccines,” James A. Mansi, PhD, the global medical lead for medical affairs at Seqirus, told Infectious Diseases in Children. “With MF59, we were able to stimulate a greater immune response against a broader repertoire of antigen — and this persists through and beyond the influenza season.”
Results of a randomized controlled trial — published earlier this year in The Lancet Respiratory Medicine — demonstrated that vaccination with aQIV in children aged 6 months to 5 years resulted in enhanced immunogenicity during an influenza season in which there was a significant mismatch between strains contained in the vaccine and circulating strains. More than 600 of these children were invited back the following year for repeat vaccination.
The participants, who at that point were aged 1 to 6 years, were given the same vaccine they had received in the parent study — aQIV or a nonadjuvanted vaccine. The researchers collected blood samples from the children at baseline, 22 days and 180 days after vaccination.
Children’s improved immune responses persisted from the previous year, researchers said. At baseline, those who received aQIV during the parent study had significantly greater geometric mean titer (GMT) values against all four homologous strains compared with children who received an unadjuvanted vaccine.
After the second year of vaccination, the aQIV group met criteria established by the Center for Biologics Evaluation and Research regarding seroconversion and hemagglutination inhibition (HI) titer (1:40) for all four homologous strains that were tested on day 22.
“When we immunized these children in the second season with the adjuvanted quadrivalent vaccine, this benefit of a higher and more broad response accrues,” Mansi said. “And by that, I mean we can build upon it after repeated vaccination in the subsequent year.”
At both day 22 and day 181, children who received aQIV had significantly greater GMT values for HI against all four homologous strains vs. children in the nonadjuvanted group. Children in the aQIV group also had increased immune responses against selected heterologous strains that were tested at baseline, day 22 and day 181.
“These children are essentially generating antibodies beyond what’s contained in the vaccine,” Mansi said, “and this is important simply because of the unpredictable nature of influenza. With the MF59 adjuvant, these children were able to generate a broader immune response so they are better prepared, better armed, with a more diverse population of antibodies to respond to antigenic drifts.”
Regarding safety, more children in the aQIV group experienced transient and generally mild to moderate reactogenicity, but the overall safety profiles were similar between the two groups, the researchers said.
In the past, some circulating strains, such as H3N2 during last year’s influenza season, have eluded egg-based vaccines. Although adjuvants have been effective at increasing cross-reactivity against viral strains that are not included in the vaccine, Mansi said his company wants to combine the MF59 adjuvant with cell-based vaccine technology to provide even greater protection in children.
“We’ll be redirecting our resources toward what I think is a real paradigm shift by combining both of our innovative technologies — our cell culture and our adjuvanted platform,” he said, “and this brings the best of these two platforms together.” – by John Schoen
Daly W, et al. Abstract 987. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.
Disclosure: Mansi is employed by Seqirus, which sponsored the study.