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 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 < 0·01). Both strength elicited neutralising activity against the SARS-CoV-2, specifically (18·3; 95% CI 14·7-22·78) for Abdala 25 µg and (36·4; 95% CI 30·26-43·8) for 50 µg 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. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Contaminación cruzada por Mycobacterium tuberculosis en el Laboratorio Nacional de Referencia de Tuberculosis de Cuba / Cross-contamination of Mycobacterium tuberculosis at the National Rference Laboratory of Tuberculosis of Cuba

Introducción: la contaminación cruzada por Mycobacterium tuberculosis (Mtb) en el laboratorio es más común de lo que se piensa.Objetivo: confirmar un posible episodio de contaminación cruzada por Mtb en el Laboratorio Nacional de Referencia de Tuberculosis, Lepra y Micobacterias del Instituto Pedro Kouri.Métodos: se realizó un estudio descriptivo y retrospectivo de los indicadores de calidad del cultivo del 3er trimestre de 2014. Se observó un incremento de cultivos positivos a Mtb con codificaciones bajas, durante un día de trabajo. Se encontraron 10 aislamientos de 19 muestras procesadas: ocho con sospecha de contaminación cruzada y dos aislamientos pertenecientes a uno de los pacientes involucrados y que tuvo un cultivo positivo procesado en una fecha diferente. Las muestras se procesaron según lo establecido por el Programa Nacional de Control de la Tuberculosis de Cuba. A los cultivos positivos se les realizó la tipificación con oligonucleótidos espaciadores Spoligotyping.Resultados: el aislamiento de la muestra 1 435 (paciente 1) fue un patrón único al no aparecer en la base de datos internacional SITVIT2. En los cultivos de las muestras 1 438 y 1 439 (paciente 2) se identificó el linaje Beijing (tipo 1). En los siete cultivos restantes (pacientes del 3 al 7) se identificó el linaje S tipo 71; los cultivos posteriores de estos pacientes fueron negativos a excepción del paciente 5 (muestra 1 561), en el que se aisló Mtb con el mismo patrón genético.Conclusiones: los resultados de la genotipificación permitieron confirmar los cultivos positivos contaminados e inferir una posible fuente de contaminación durante ese día de trabajo. También resalta la importancia de identificar eventos de contaminación cruzada, pues puede implicar un mal manejo clínico de los pacientes, así como el uso innecesario de un tratamiento largo y costoso, además de influir en el análisis e interpretación de los resultados desde el punto de vista epidemiológico(AU)

Introduction: cross contamination of Mycobacterium tuberculosis in the laboratory is more common than thought.Objective: to confirm a possible event of cross-contamination of Mycobacterium tuberculosis in the National Reference Laboratory of Tuberculosis, Leprosy and Mycobacteria of Pedro Kouri Institute.Methods: a descriptive and retrospective study of quality indicators of culture for the third quarter of 2014 was conducted. An increased Mycobacterium tuberculosis-positive culture with low encodings was observed during a working day. Ten isolates of 19 processed samples were found: eight suspected cross-contamination and two isolates from one of the patients involved and had a positive culture processed on a different date. The samples were processed as established by the National Program for Tuberculosis Control in Cuba .Positive cultures were typed by using oligonucleotide spacers Spoligotyping.Results: the isolation of the sample 1 435 (patient 1) showed a unique pattern that does not appear in the international database SITVIT2. In the culturing of 1 438 and 1 439 samples (patient 2), the Beijing lineage (type 1) was identified. In the remaining seven cultures (patients 3 through 7), the lineage S type 71 was identified. The subsequent cultures of the samples taken from these patients were negative except for patient 5 (sample 1 561) in whom Mtb was isolated with the same genetic pattern.Conclusions: the results of genotyping allowed confirming the contaminated positive cultures and inferring a possible source of contamination during that workday. It also highlights the importance of identifying cross-contamination events, because it may involve poor clinical management of patients and thus the unnecessary use of a long and costly treatment, in addition to influencing the analysis and interpretation of the results from the epidemiological viewpoint(AU)

Contaminación cruzada por Mycobacterium tuberculosis en el Laboratorio Nacional de Referencia de Tuberculosis de Cuba / Cross-contamination of Mycobacterium tuberculosis at the National Rference Laboratory of Tuberculosis of Cuba

Introducción: la contaminación cruzada por Mycobacterium tuberculosis (Mtb) en el laboratorio es más común de lo que se piensa. Objetivo: confirmar un posible episodio de contaminación cruzada por Mtb en el Laboratorio Nacional de Referencia de Tuberculosis, Lepra y Micobacterias del Instituto Pedro Kouri. Métodos: se realizó un estudio descriptivo y retrospectivo de los indicadores de calidad del cultivo del 3er trimestre de 2014. Se observó un incremento de cultivos positivos a Mtb con codificaciones bajas, durante un día de trabajo. Se encontraron 10 aislamientos de 19 muestras procesadas: ocho con sospecha de contaminación cruzada y dos aislamientos pertenecientes a uno de los pacientes involucrados y que tuvo un cultivo positivo procesado en una fecha diferente. Las muestras se procesaron según lo establecido por el Programa Nacional de Control de la Tuberculosis de Cuba. A los cultivos positivos se les realizó la tipificación con oligonucleótidos espaciadores Spoligotyping. Resultados: el aislamiento de la muestra 1 435 (paciente 1) fue un patrón único al no aparecer en la base de datos internacional SITVIT2. En los cultivos de las muestras 1 438 y 1 439 (paciente 2) se identificó el linaje Beijing (tipo 1). En los siete cultivos restantes (pacientes del 3 al 7) se identificó el linaje S tipo 71; los cultivos posteriores de estos pacientes fueron negativos a excepción del paciente 5 (muestra 1 561), en el que se aisló Mtb con el mismo patrón genético. Conclusiones: los resultados de la genotipificación permitieron confirmar los cultivos positivos contaminados e inferir una posible fuente de contaminación durante ese día de trabajo. También resalta la importancia de identificar eventos de contaminación cruzada, pues puede implicar un mal manejo clínico de los pacientes, así como el uso innecesario de un tratamiento largo y costoso, además de influir en el análisis e interpretación de los resultados desde el punto de vista epidemiológico(AU)

Introduction: cross contamination of Mycobacterium tuberculosis in the laboratory is more common than thought. Objective: to confirm a possible event of cross-contamination of Mycobacterium tuberculosis in the National Reference Laboratory of Tuberculosis, Leprosy and Mycobacteria of Pedro Kouri Institute. Methods: a descriptive and retrospective study of quality indicators of culture for the third quarter of 2014 was conducted. An increased Mycobacterium tuberculosis-positive culture with low encodings was observed during a working day. Ten isolates of 19 processed samples were found: eight suspected cross-contamination and two isolates from one of the patients involved and had a positive culture processed on a different date. The samples were processed as established by the National Program for Tuberculosis Control in Cuba .Positive cultures were typed by using oligonucleotide spacers Spoligotyping. Results: the isolation of the sample 1 435 (patient 1) showed a unique pattern that does not appear in the international database SITVIT2. In the culturing of 1 438 and 1 439 samples (patient 2), the Beijing lineage (type 1) was identified. In the remaining seven cultures (patients 3 through 7), the lineage S type 71 was identified. The subsequent cultures of the samples taken from these patients were negative except for patient 5 (sample 1 561) in whom Mtb was isolated with the same genetic pattern. Conclusions: the results of genotyping allowed confirming the contaminated positive cultures and inferring a possible source of contamination during that workday. It also highlights the importance of identifying cross-contamination events, because it may involve poor clinical management of patients and thus the unnecessary use of a long and costly treatment, in addition to influencing the analysis and interpretation of the results from the epidemiological viewpoint(AU)