Search

Summary: 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 Camagüey, 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 μg or 50 μg 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 per-protocol 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 [8·4%] of 1707 total doses applied), taking place in 66/851 (7·8%) in the 25 μg group and in 77/856 (9·0%) in the 50 μg. The most common systemic adverse event (AE) was headache: 23/851 (2·7%) in the 25 μg group and 19/856 (2·2%) in the 50 μg. 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 98·2% of the children and adolescents (231/234) for the 50 μg group and 98·7% (224/228) for the 25 μg group without differences between both strength. The specific IgG antibody geometric mean titres (GMT) showed higher titres between participants who received Abdala 50 μg (231·3; 95% CI 222·6–240·4) compared to those who received 25 μg (126·7; 95% CI 121·9–131·7). The mean ACE2 inhibition %, were 59·4% for 25 μg, and for 50 μg, 72·9% (p

Summary: Background: Multiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity protein of a novel SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 1-2, randomised, double-blind, placebo-controlled trial was carried out in “Saturnino Lora” Hospital, Santiago de Cuba, Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1:1, in blocks) to three groups: placebo, 25 µg and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0·5 mL in the deltoid region. During the first phase, two immunization schedules were studied: 0-14-28 days (short) and 0-28-56 days (long). In phase 2, only the short schedule was evaluated. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained masked during the study period. The main endpoints were safety and the proportion of subjects with seroconversion of anti-RBD IgG antibodies, analysed by intention to treat and per protocol, respectively. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000346. Findings: Between Dec 7, 2020, and Feb 9, 2021, 792 subjects were included; 132 (66 in each vaccination schedule, divided into 22 for each group) in phase 1, and 660 (220 in each group plus 66 from the short scheme of phase 1) in phase 2. The product was well tolerated. No severe adverse events were reported. During phase 1, the incidence of adverse events in the 25 µg, 50 µg, and placebo arms for the short schedule were 6/22 (27·3%), 6/22 (27·3%), 3/22 (13·6%), respectively, and for the long schedule were 8/22 (36·4%), 9/22 (40·9%), 4/22 (18·2%), respectively. In phase 2, adverse reactions were reported by 53/242 (21·9%), 75/242 (31·0%) and 41/242 (16·9%) participants in the 25 µg, 50 µg, and placebo group, respectively. Adverse reactions were minimal, mostly mild, and from the injection site, which resolved in the first 24-48 hours. In phase 1, seroconversion at day 56 was seen in 95·2% of the participants (20/21) in the 50 μg group, 81% (17/21) in the 25 μg group, and none in the placebo group (0/22). For the long schedule, seroconversion at day 70 was seen in 100% of the participants (21/21) in the 50 μg group, 94·7% (18/19) in the 25 μg group, and none in the placebo group (0/22). In phase 2, seroconversion of anti-RBD IgG antibodies at day 56 was seen in 89·2% of the participants in the 50 μg group (214/240; 95% CI 84·5-92·82), 77·7% in the 25 μg group (185/238; 72·0-82·9) and 4·6% in the placebo group (11/239; 2·3-8·1). Compared with the placebo arm, the differences in the proportion of participants with seroconversion were 73·1% (95% CI 66·8-79·5) and 84·6% (79·4-89·7) in the 25 μg and 50 μg groups, respectively. The seroconversion rate in the 50 μg group was significantly higher than in the 25 μg group (p=0·0012). Interpretation: The Abdala vaccine was safe, well tolerated, and induced humoral immune responses against SARS-CoV-2. These results, in the context of the emergency COVID-19 pandemic, support the 50 μg dose, applied in a 0-14-28 days schedule, for further clinical trials to confirm vaccine efficacy. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Introduction: The clinical evaluation of anti-COVID-19 vaccines in pediatric population, is a challenge in times of pandemic, to respond to the urgency of representative samples that contribute to the reproducibility of the study in the real population. Objective: To characterize the adolescents participating in the clinical trial with the Abdala anti-COVID-19 vaccine, to evaluate compliance with the vaccination schedule and to estimate whether they are representative of this population group. Methods: Data from a phase II trial with Abdala vaccine were used. A total of 703 subjects were included, 207 (29.4 %) of them were adolescents, between 12 and 18 years of age, with apparently healthy or controlled chronic diseases, nutritional assessment between 10 and 90 percentiles, and willingness to participate in the study. Sociodemographic data, personal pathological history, toxic habits and compliance with the vaccination scheme of 3 doses every 14 days were the variables studied. Results: The average age was 15 years, it was predominant female sex (51.7 %), white skin color (55.6 %) and nutritional assessment above 75 to 90 percentiles (40.6 %). The 9.6 % had toxic habits such as smoking and ingestion of alcoholic beverages. Some personal pathological history was in 51.2 % with a higher prevalence for bronchial asthma, rhinitis and other allergies. The vaccination scheme was fulfilled for 95.8 % of individuals. Conclusions: Sociodemographic characteristics, pathological history and toxic habits described for adolescents on the study are representative for this population group in Cuba. The vaccination schedule had an optimal compliance.