An analysis today of pooled data from five US surveillance studies across three flu seasons in children found that the inhaled quadrivalent live attenuated influenza vaccine (LAIV) wasn't as effective as the injectable version of the vaccine against the 2009 H1N1 strain.
The nasal spray flu vaccine, first licensed in 2003, is back on the market this flu season with a new 2009 H1N1 vaccine component, following a 2-year hiatus, during which federal vaccine advisors grappled with studies showing a drop in protection.
Interpretation of the earlier studies, all conducted in outpatient settings, was hampered by small sample sizes. For example, the individual studies weren't able to tease out possible differences by age or previous-season vaccination. Today's study, led by researchers at the US Centers for Disease and Prevention (CDC), appears in Pediatrics.
Age-group, prior vaccine didn't explain differences
Researchers looked at data from five US studies conducted from the 2013-14 through 2015-16 seasons comparing quadrivalent LAIV and the inactivated influenza vaccine (IIV) against lab-confirmed flu in children ages 2 to 17. Factors included influenza season, subtype, age-group, and prior vaccination status. They calculated vaccine effectiveness (VE) for LAIV and IIV based on a test-negative study design.
Of 17,173 patients from the five studies, 4,579 received IIV, 1,979 received LAIV, and 10,615 were unvaccinated. For IIV, VE was 67% against the 2009 H1N1 virus (95% confidence interval [CI], 62% to 72%. For LAIV, however, VE against the same strain was 20% (95% CI, -6% to 39%) and not statistically significant.
The reduced effectiveness the scientists found for LAIV applied to all age-groups. Results were similar in children vaccinated the previous season, meaning that prior vaccination status didn't explain the VE difference.
Compared with their IIV peers, kids who got quadrivalent LAIV has significantly higher odds of contracting 2009 H1N1 (odds ratio, 2.66; 95% CI, 2.06 to 3.44).
Both vaccines, though, had similar effectiveness against H3N2 and influenza B. During the 2014-15 season dominated by a drifted H3N2 strain, VE was poor for both vaccines, regardless of previous season vaccination.
The authors of the study wrote that the overall findings were consistent by flu season and age-group and that the reduced VE they saw for LAIV against the 2009 H1N1 virus was similar to earlier published findings from the individual studies.
Can FluMist recapture its past performance?
In a related commentary in the same issue of Pediatrics, Pedro Piedra, MD, with the departments of molecular virology and microbiology and pediatrics at Baylor College of Medicine in Houston, wrote that overall, the five surveillance studies underscore the CDC Advisory Committee on Immunization Practices (ACIP) recommendations against LAIV use during the 2016-17 and 2017-18 flu seasons.
He said the trivalent version of LAIV had much higher VE in children against seasonal H1N1, including new variants, which even prompted ACIP to issue a preferential recommendation for children ages 2 to 8 for the 2014-15 season.
"This begs the question, 'Why did LAIV4 vaccine effectiveness performance decline, and can it recapture its past performance when it was a trivalent formulation?' " Piedra wrote, noting that vaccine shipment handling, characteristics of the 2009 H1N1 vaccine strain, preexisting immunity, and viral interference by adding a second influenza B strain were all considered.
AstraZeneca, the maker of FluMist, has updated the 2009 H1N1 strain to influenza A/Slovenia/2903/2015, which has improved viral growth, he said, and last year ACIP recommended quadrivalent LAIV as an option, based on viral shedding data and immunogenicity in young children.
Piedra said since then, the United Kingdom—which has a universal flu vaccine program for kids that mainly uses LAIV—has released an interim analysis for the 2017-18, which suggested an adjusted VE of 90.3% (95% CI, 16.4% to 98.9%) against 2009 H1N1.
"This early result is encouraging and supports the reintroduction of LAIV4 in the United States as an option for the control of seasonal influenza," he wrote, adding that the results highlight the value of annual influenza VE estimates and the important role the US Influenza vaccine Effectiveness Network plays in providing ACIP with new information for its work on recommendations.
Jan 7 Pediatrics abstract
Jan 7 Pediatrics commentary