Comparative assessment of immunogenicity and safety of recombinant influenza vaccine in children, adolescents, and adults: results from a phase 3, immunobridging, open-label, non-randomised study

Abstract

Background: The recombinant influenza vaccine (RIV) is licensed for adults older than 18 years but is not approved for paediatric groups. This study aimed to demonstrate the non-inferior immune responses and safety of RIV in participants aged 9-17 years compared with adults aged 18-49 years.

Methods: This was a phase 3, non-randomised, immunobridging, open-label, uncontrolled study conducted at 36 centres in Europe and the USA during the 2022-23 northern hemisphere influenza season. The main exclusion criteria were receipt of an influenza vaccine up to 6 months before enrolment and receipt of any other vaccines within 4 weeks before or after study intervention (except for COVID-19 vaccination, which was allowed at least 2 weeks before or after enrolment). Healthy participants aged 9-49 years received a single dose of quadrivalent RIV and were followed up for 6 months on days 9, 29, and 181. Haemagglutination inhibition (HAI) assays to assess immunogenicity were used to test blood samples obtained at baseline and day 29. The primary outcome was the non-inferiority of immune response at day 29 as assessed by HAI titre ratios and differences in seroconversion rates between the two age groups. The non-inferiority of a geometric mean titre was demonstrated if the lower limit of the two-sided 95% CI of the geometric mean titre (GMT) ratio was above 0·667 for each of the four strains of virus. Similarly, the non-inferiority of seroconversion was demonstrated if the lower limit of the two-sided 95% CI was -10% or above for each of four strains. Safety was monitored throughout the study. This study was registered at ClinicalTrials.gov (NCT05513053) and is complete.

Findings: Between Oct 27, 2022, and May 1, 2023, a total of 1308 participants were enrolled, all of whom attended the first study visit. 1299 participants (99%) received the study vaccine (641 participants [49%] in the age 9-17 years group and 658 participants [51%] in the age 18-49 years group). The mean age of participants in the age 9-17 years group was 13·0 years (SD 2·5) and was 34·3 years (9·2) in the age 18-49 years group. Overall, 707 participants (54%) were female and 601 participants (46%) were male. Most of the participants were White (1003 [77%] of 1308); the next largest category was Black or African American (255 [19%]); 149 (11%) participants identified as Hispanic or Latino. The HAI GMT ratio between the paediatric and adult groups at day 29 in the per-protocol analysis set was 2·0 (95% CI 1·7 to 2·3), 3·3 (2·8 to 3·9), 1·6 (1·4 to 1·8), and 1·2 (1·1 to 1·4) for A/H1N1, H3N2, B/Victoria, and B/Yamagata, respectively. Differences in seroconversion between the groups were 1·9 (-2·8 to 6·6), -0·6 (-4·4 to 3·2), 3·3 (-1·6 to 8·1), and 14·3 (9·2 to 19·3) for each of the four strains, respectively. The safety profile was comparable in both age groups, except for solicited reactions within 7 days post-vaccination that were fewer in children and adolescents (274 [44%] of 618; 95% CI 40 to 48) than in adults (336 [53%] of 635; 49 to 57). No related serious adverse events, deaths, or adverse events of special interest were reported.

Interpretation: RIV4 induced non-inferior immune responses in the participants aged 9-17 years compared with those aged 18-49 years. No safety concerns were reported.

Funding: Sanofi.