Immunogenicity and safety assessment of a SARS-CoV-2 recombinant spike RBD protein vaccine (Abdala) in paediatric ages 3-18 years old: a double-blinded, multicentre, randomised, phase 1/2 clinical trial (ISMAELILLO study)

Background COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population. Methods A double-blinded, multicentre, randomised, phase 1/2 clinical trial was conducted in nine polyclinics in the province of Camaguey, Cuba. Healthy children and adolescents were stratified according to age (3-11 years old, or 12-18 years old) and they were randomly assigned (1:1; block size four) in two dosage level groups of vaccine to receive three intramuscular doses of 25 mu g or 50 mu g of RBD, 14 days apart. Main safety endpoint was analyzed as the percentage of serious adverse reactions during vaccination up to 28 days after the third dose (Day 56) in participants who received at least one dose vaccination. The primary immunogenicity endpoint assessed was seroconversion rate of anti-RBD IgG antibody at day 56. The immunogenicity outcomes were assessed in the perprotocol population. This trial is registered with Cuban Public Registry of Clinical Trials, RPCEC00000381. Findings Between July 15, 2021, and August 16, 2021, 644 paediatric subjects were screened, of whom 592 were enrolled after verifying that they met the selection criteria: firstly 88 were included in Phase 1 of the study and 504 who completed Phase 2. The vaccine was well tolerated. Injection site pain was the most frequently reported local event (143 [8 center dot 4%] of 1707 total doses applied), taking place in 66/851 (7 center dot 8%) in the 25 mu g group and in 77/856 (9 center dot 0%) in the 50 mu g. The most common systemic adverse event (AE) was headache: 23/851 (2 center dot 7%) in the 25 mu g group and 19/ 856 (2 center dot 2%) in the 50 mu g. Reactogenicity was mild or moderate in severity, represented in 75% of cases by local symptoms, completely resolved in the first 24-48 h. Twenty-eight days after the third dose, seroconversion anti-RBD IgG were observed in 98 center dot 2% of the children and adolescents (231/234) for the 50 mu g group and 98 center dot 7% (224/228) for the 25 mu g group without differences between both strength. The specific IgG antibody geometric mean titres (GMT) showed higher titres between participants who received Abdala 50 mu g (231 center dot 3; 95% CI 222 center dot 6-240 center dot 4) compared to those who received 25 mu g (126 center dot 7; 95% CI 121 center dot 9-131 center dot 7). The mean ACE2 inhibition %, were 59 center dot 4% for 25 mu g, and for 50 mu g, 72 center dot 9% (p < 0 center dot 01). Both strength elicited neutralising activity against the SARS-CoV-2, specifically (18 center dot 3; 95% CI 14 center dot 7-22 center dot 78) for Abdala 25 mu g and (36 center dot 4; 95% CI 30 center dot 26-43 center dot 8) for 50 mu g to the selected sample analyzed. Interpretation Abdala vaccine was safe and well tolerated at both antigenic strength levels tested in participants aged between 3 and 18 years. Regarding immunogenicity, Abdala Vaccine stimulated the production of specific IgG antibodies against the RBD of SARS-CoV-2 as well as the production of ACE2 inhibition titres and neutralising antibodies (Nab) in children and adolescents.