Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non- inferiority, single-centre study

Background Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac).Methods We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0 & BULL;1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0 & BULL;3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0 & BULL;5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97 & BULL;5% CI with a non-inferiority margin of 0 & BULL;67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. Findings Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10 & BULL;2 [95% CI 8 & BULL;0-13 & BULL;1]; p<0 & BULL;0001).Interpretation Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents.

Automated summary

This study aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 vaccine in children and adolescents who had received two doses of inactivated vaccine. The results showed that AAd5 vaccine is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents.