Efficacy of a Cell-Based Influenza Vaccine in Children

Abstract

Source: Nolan T, Fortanier AC, Leav B, et al. Efficacy of a cell-culture-derived quadrivalent influenza vaccine in children. N Engl J Med. 2021;385(16):1485-1495; doi:10.1056/NEJMoa2024848Investigators from multiple institutions conducted a randomized controlled trial to assess the efficacy of a cell-culture-derived quadrivalent inactivated influenza vaccine (IIV4c). Children ages 2 to <18 years from 8 countries: Australia, the Philippines, Thailand, Estonia, Finland, Lithuania, Poland, and Spain, were enrolled from May 25, 2017 to November 5, 2018 and followed during a total of 3 influenza seasons. At enrollment, participants were randomized to receive IIV4c, or a noninfluenza vaccine (meningococcal ACWY [Groups A, C, W-135, and Y] vaccine) as a control. IIV4c was derived from virus grown on Madin-Darby canine kidney cell lines and included 15 µg of hemagglutinin for 2 influenza A subtypes (H1N1 and H3N2) and 2 influenza B lineages (Yamagata and Victoria) per 0.5 mL dose. Parents of participants were contacted weekly and asked about symptoms consistent with influenza-like illness in their child (temperature ≥37.8°C and at least 1 of the following: cough, sore throat, nasal congestion, or rhinorrhea). A nasal swab was obtained on those with influenza-like illness and tested for influenza by PCR and culture. The primary outcome was first occurrence of influenza, confirmed by PCR and/or culture, occurring >14 days after the last vaccination until the end of the influenza season. Secondary outcomes included occurrence of specific influenza subtypes. Cox proportional-hazards models were used to compare occurrence of influenza in those randomized to IIV4c or the control vaccine; age, country, influenza season, and influenza vaccination history were included in the models. Vaccine efficacy was estimated as 1 minus the hazard ratio.A total of 4,514 participants with a mean age of 8.8 ± 4.1 years were enrolled; 50.7% were <9 years old. Among these children, 65.9% were previously vaccinated against influenza. Outcome data were analyzed on 4,509 participants. Overall, a total of 2,186 influenza-like illnesses were reported in 1,576 participants. Nasal swabs for PCR and culture were obtained during 97.4% of these illnesses, and first occurrence of influenza was confirmed in 539 participants, including 231 cases of influenza B (42.9%), 162 cases of influenza A/H3N2 (30.1%), and 126 of influenza A/H1N1 (23.4%). Among those randomized to IIV4c, influenza occurred in 175 of 2,257 participants (7.8%) vs 364 of 2,252 (16.2%) of those randomized to meningococcal ACWY. Overall efficacy of IIV4c was estimated at 54.6% (95% CI, 45.7, 62.1), 58.7% (95% CI, 47.5, 67.5) in children previously vaccinated, and 48.4% (95% CI, 32.1, 60.8) in those previously unvaccinated. Efficacy against A/H1N1, A/H3N2, and type B were 80.7% (95% CI, 69.2, 87.9), 42.1% (95% CI, 20.3, 57.9) and 47.6% (95% CI, 31.4, 60.0), respectively.The authors conclude that IIV4c was effective in preventing influenza.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Most pediatric influenza vaccines in the US are manufactured using virus strains grown in eggs (egg-based).1 During growth in eggs, an influenza virus may undergo mutations in the globular head of the hemagglutinin protein, the major epitope.2 Antibodies to the hemagglutinin elicited by egg-based vaccine strains may fail to recognize the hemagglutinin of wild-type influenza strains, even when the vaccine strains and circulating strains are well-matched.3 This has led to low influenza vaccine effectiveness, especially of the H3N2 vaccine strain, in recent seasons.2 Another disadvantage of egg-based influenza vaccines is the long response time to manufacture vaccines when a new influenza virus emerges.4The IIV4c vaccine has been available for adults and children ≥4 years old since 2016.5 In March 2021, approval was extended to children ≥2 years old based on efficacy data from the current study. In October 2021, approval was further extended to infants ≥6 months based on data from a phase 3 randomized controlled study of children aged 6-47 months.6,5Much of the world is still in the throes of a coronavirus pandemic.7 Influenza also has the potential to cause pandemics, which are difficult to predict.1 Newer vaccine platforms (eg, mRNA vaccines as used in SARS-CoV-2 vaccine development) may offer additional protection against influenza.7Cell-culture-derived influenza vaccines have been approved for children ≥6 months. They are safe and effective in preventing influenza in healthy children. (See AAP Grand Rounds. 2022;47[1]:3).8