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Abdala is a recently released RBD protein subunit vaccine against SARS-CoV-2. A few countries, including Mexico, have adopted Abdala as a booster dose in their COVID-19 vaccination schemes. Despite that, most of the Mexican population has received full-scheme vaccination with platforms other than Abdala; little is known regarding Abdala's immunological features, such as its antibody production and T- and B-cell-specific response induction. This work aimed to study antibody production and the adaptive cellular response in the Mexican population that received the Abdala vaccine as a booster. We recruited 25 volunteers and evaluated their RBD-specific antibody production, T- and B-cell-activating profiles, and cytokine production. Our results showed that the Abdala vaccine increases the concentration of RBD IgG-specific antibodies. Regarding the cellular response, after challenging peripheral blood cultures with RBD, the plasmablast (CD19+CD27+CD38High) and transitional B-cell (CD19+CD21+CD38High) percentages increased significantly, while T cells showed an increased activated phenotype (CD3+CD4+CD25+CD69+ and CD3+CD4+CD25+HLA-DR+). Also, IL-2 and IFN-γ increased significantly in the supernatant of the RBD-stimulated cells. Our results suggest that Abdala vaccination, used as a booster, evokes antibody production and the activation of previously generated memory against the SARS-CoV-2 RBD domain.
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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.
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El texto presta atención las condicionantes sociales principales de la obtención de la vacuna Abdala como proceso social. El primero, histórico fundacional, se relaciona con la actitud científica del médico cubano Tomás Romay y Chacón ante el conocimiento y la práctica de la medicina; el segundo, político de partida, tiene que ver con importantes decisiones políticas tomadas por el gobierno revolucionario cubano a partir de 1959 que sentaron las bases para las políticas públicas de ciencia, tecnología e innovación; el tercero, educativo revolucionario, más cercano en el tiempo, remite a la educación patriótico-revolucionaria adquirida por quienes iniciaron la biotecnología en Cuba, que les permitió resultados relevantes en los comienzos de este campo a nivel internacional; el cuarto, organizativo tecnológico, remite a las formas organizativas innovadoras empleadas en la obtención de la vacuna Abdala. El objetivo general que se persigue es caracterizar los referidos condicionantes principales.
SUMMARY The text pays attention to four main social conditions of obtaining the Abdala vaccine as a social process. The first, foundational history, is related to the scientific attitude of the Cuban doctor Tomás Romay y Chacón towards the knowledge and practice of medicine; the second, starting political, has to do with important political decisions taken by the Cuban revolutionary government from 1959 that laid the foundations for public policies on science, technology and innovation; the third, revolutionary education, closer in time, refers to the patriotic-revolutionary education acquired by those who started biotechnology in Cuba, which allowed them to obtain relevant results at the beginning of this field at an international level; the fourth, technological organizational, refers to the innovative organizational forms used to obtain the Abdala vaccine. The general objective pursued is to characterize the aforementioned main determining factors.
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Introducción: En Cuba se desarrollan sus propias vacunas, a pesar de que el país atraviesa una gran crisis económica y los recursos materiales son limitados. Objetivo: Describir la campaña de vacunación anti-COVID-19 con Abdala en una población adulta. Métodos: Se realizó un estudio descriptivo de series de casos en 616 pacientes mayores de 19 años de edad correspondientes al Consultorio Médico de la Familia No. 5 del Policlínico Docente Ramón López Peña en Santiago de Cuba, quienes recibieron el inmunógeno Abdala de junio a agosto del 2021. Resultados: En los 616 adultos que fueron inmunizados en el vacunatorio de su consultorio médico, predominó el sexo masculino (53,4 %), sobre todo en las edades de 40 a 59 años (20,2 %). Entre los efectos secundarios más usuales figuraron el dolor en el sitio de la inyección (23,1 %), seguido de la cefalea (12,2 %); no obstante, todos completaron el esquema de vacunación de 3 dosis. En general, fue vacunado 93,6 % de la población adulta de dicho consultorio y 6,4 % no recibió la inmunización, debido principalmente al antecedente de infección por el SARS-CoV-2 (1,6 %), entre otras causas. Conclusiones: La campaña resultó exitosa, pues se alcanzó un elevado porcentaje de personas inmunizadas, lo cual se atribuye a la activa participación de la población y del equipo básico de salud.
Introduction: In Cuba our own vaccines are developed, although the country has a great economic crisis and the material resources are limited. Objective: To describe the vaccination anti-COVID-19 campaign with Abdala in an adult population. Methods: A descriptive serial cases study was carried out in 616 patients over 19 years corresponding to the Family Doctor Office No. 5 of Ramón López Peña Teaching Polyclinic in Santiago de Cuba, who received the immunogen Abdala from June to August, 2021. Results: In the 616 adults that were immunized in the vaccine office of their family doctor office, there was a prevalence of the male sex (53.4 %), mainly 40 to 59 years (20.2 %). Among the most usual secondary effects we can mention pain in the place of the injection (23.1 %), followed by headache (12.2 %); nevertheless, all completed the vaccination scheme of 3 doses. In general, the 93.6 % of the adult population was vaccinated and 6.4 % didn't receive the immunization, mainly due to the history of infection by the SARS-CoV-2 (1.6 %), among other causes. Conclusions: The campaign was successful, because a high percentage of immunized people was reached, which is attributed to the active participation of the population and the health basic team.
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Programas de Inmunización , Infecciones por Coronavirus , Vacunación MasivaRESUMEN
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.
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Background: COVID-19 vaccines that trigger a strong secretory antibody response in breast milk may achieve effective passive protection of vulnerable newborns and breastfed infants of immunized mothers. The aim of this work was to investigate the presence of SARS-CoV-2 spike RBD-specific IgA and IgG antibodies in breast milk, 5 and 9 weeks after vaccination with 3 doses of the protein subunit vaccine Abdala, compared to those found in breast milk from COVID-19-recovered women, collected at least 40 days after the infection. Methods: SARS-CoV-2 spike RBD-specific IgA and IgG antibodies were semi-quantified by indirect ELISA, using a homemade standard generated by pooling twenty breast milk samples with high absorbance values according to preliminary data. The validity of the standard curves was proved following the European Medicines Agency Guideline. Two breast milk samples from 2 unvaccinated women who had not been infected with COVID-19 were included as negative controls. Potentially neutralizing antibodies was assessed by a SARS-CoV-2 surrogate virus neutralization test. Results: High levels of anti-RBD IgA antibodies were detected in breast milk samples 9 weeks after vaccination and anti-RBD IgG antibodies rise from the fifth to the ninth week. In the post-COVID-19 time that was evaluated, the IgG-type response was notably higher compared to both post-vaccination periods. Neutralizing antibody titers were similar in breast milk from vaccinated and COVID-19 recovered women. Conclusions: This is the first report about the immune response in breast milk after the administration of a COVID-19 protein subunit vaccine, which could provide analogous protection to that conferred by SARS-CoV-2 infection. This implies a potential passive immunity that breastfed infants receive from their mothers vaccinated with Abdala.