Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma.

BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.

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.

Design of a culture medium for optimal growth of the bacterium Pseudoxanthomonas indica H32 allowing its production as biopesticide and biofertilizer.

Culture medium composition is one of the most important parameters to analyze in biotechnological processes with industrial purposes. The aim of this study was to design of a culture medium for optimal growth of the bacterium Pseudoxanthomonas indica H32 allowing its production as biopesticide and biofertilizer. The influence of several carbon and nitrogen sources and their molar ratios on P. indica H32 growth was investigated. The effect of different micronutrients such as mineral salts and vitamin on P. indica H32 growth was determined as well. A mixture design based on Design-Expert 10.0 Software was performed to optimize the culture medium concentration. Finally, in the designed medium, an attribute of the biological mechanism of action of the P. indica H32 against nematodes, was evaluated: the hydrogen sulfide production. It was found that tested carbon/nitrogen ratios were not a significant influence on P. indica H32 growth. Growth of P. indica H32 was favored with use of sucrose, yeast extract and phosphate buffer without the addition of any tested micronutrients. An optimal concentration of 10 g/L sucrose and 5 g/L yeast extract were obtained at a cost of 0.10 $/L. In this concentration, the specific growth rate (µ) and maximal optical density (Xmax) were equal to 0.439 h- 1 and 8.00 respectively. It was evidenced that under the culture conditions used, P. indica H32 produced hydrogen sulfide. The designed medium led to a 1.08 $/L reduction of costs in comparison to LB medium. These results were critical to carry on with biotechnological development of P. indica H32 as a bioproduct.

Metodología de evaluación del impacto social de un programa de salud / Assessment methodology of social impact for a health program

El artículo tiene como objetivo exponer los fundamentos en que se sustenta la metodología de evaluación de impacto social de un programa de salud con vistas a mejorar la calidad de los servicios en el sector. El producto científico presentado muestra el análisis y síntesis de documentos a partir de la bibliografía actualizada publicada en revistas digitales como Salud Pública Cubana; libros y materiales de autores de reconocido prestigio. La propuesta contempla cuatro etapas fundamentales, cuyas bases teóricas fueron asumidas de investigaciones con este objeto de estudio en el contexto nacional e internacional(AU)

This article aims at setting out the fundamentals that support the assessment methodology of social impact of a health program in order to improve the quality of health care services provided in the sector. The scientific product presented shows the analysis and synthesis of documents starting from updated bibliography published in digital journals such as Cuban Public Health; books and materials from prestigious authors. The proposal has four main stages which theoretical basis were taken from researches with the same object of study in a national and international context(AU)

Metodología de evaluación del impacto social de un programa de salud / Assessment methodology of social impact for a health program

El artículo tiene como objetivo exponer los fundamentos en que se sustenta la metodología de evaluación de impacto social de un programa de salud con vistas a mejorar la calidad de los servicios en el sector. El producto científico presentado muestra el análisis y síntesis de documentos a partir de la bibliografía actualizada publicada en revistas digitales como Salud Pública Cubana; libros y materiales de autores de reconocido prestigio. La propuesta contempla cuatro etapas fundamentales, cuyas bases teóricas fueron asumidas de investigaciones con este objeto de estudio en el contexto nacional e internacional.

This article aims at setting out the fundamentals that support the assessment methodology of social impact of a health program in order to improve the quality of health care services provided in the sector. The scientific product presented shows the analysis and synthesis of documents starting from updated bibliography published in digital journals such as Cuban Public Health; books and materials from prestigious authors. The proposal has four main stages which theoretical basis were taken from researches with the same object of study in a national and international context.

Aspectos sociales de la aplicación del Heberprot-P en el servicio de Angiología del Hospital Manuel Ascunce Doménech / Social aspects of the application of the Heberprot-P in the Angiology service at Manuel Ascunce Domenech Hospital

En la actualidad Cuba desarrolla un Programa de Atención Integral al Paciente con Úlcera de Pie Diabético (UPD) mediante el uso del Heberprot-P, esencial para disminuir la amputación y la discapacidad. El trabajo tiene el objetivo de realizar un diagnóstico sobre la aplicación del Heberprot-P en el Servicio de Angiología del Hospital Provincial Universitario Manuel Ascunce Domenech de Camagüey. Se realizaron encuestas a pacientes para identificar necesidades sentidas relacionadas con el tratamiento y para las actitudes manifiestas, y se hicieron entrevistas al personal médico y de enfermería. El diagnóstico permitió corroborar la necesaria investigación con enfoque social del servicio de salud escogido a nivel territorial. Destaca elevar el trabajo de captación de pacientes desde el nivel primario de salud para garantizar un mayor alcance del programa, así como la trascendencia del apoyo familiar y la relación profesional de la salud- paciente a fin de lograr la calidad requerida (AU)

At present Cuba is developing a program concerning the care of patient with ulcer of the diabetes foot by means of Heberprot-P essential to reduce the amputation and disability. The aim of this paper is to carry out a diagnosis about social aspects of the application of the Heberprot-P in the Angiology service at Manuel Ascunce Domenech Hospital in Camaguey. Some surveys were carry out to identify certain needs related with the treatment and the attitude shown and on the other hand some interview were made to the medical and nursing staff. The diagnosis allowed to verify the need of the research with social approach. The paper highlight how to incorporate patients from the primary health level, in order this program has a higher scope and the importance of the family support and the professional relationship to accomplish the quality required (AU)

Aspectos sociales de la aplicación del Heberprot-P en el servicio de Angiología del Hospital Manuel Ascunce Doménech / Social aspects of the application of the Heberprot-P in the Angiology service at Manuel Ascunce Domenech Hospital

En la actualidad Cuba desarrolla un Programa de Atención Integral al Paciente con Úlcera de Pie Diabético (UPD) mediante el uso del Heberprot-P, esencial para disminuir la amputación y la discapacidad. El trabajo tiene el objetivo de realizar un diagnóstico sobre la aplicación del Heberprot-P en el Servicio de Angiología del Hospital Provincial Universitario Manuel Ascunce Domenech de Camagüey. Se realizaron encuestas a pacientes para identificar necesidades sentidas relacionadas con el tratamiento y para las actitudes manifiestas, y se hicieron entrevistas al personal médico y de enfermería. El diagnóstico permitió corroborar la necesaria investigación con enfoque social del servicio de salud escogido a nivel territorial. Destaca elevar el trabajo de captación de pacientes desde el nivel primario de salud para garantizar un mayor alcance del programa, así como la trascendencia del apoyo familiar y la relación profesional de la salud- paciente a fin de lograr la calidad requerida.

At present Cuba is developing a program concerning the care of patient with ulcer of the diabetes foot by means of Heberprot-P essential to reduce the amputation and disability. The aim of this paper is to carry out a diagnosis about social aspects of the application of the Heberprot-P in the Angiology service at Manuel Ascunce Domenech Hospital in Camaguey. Some surveys were carry out to identify certain needs related with the treatment and the attitude shown and on the other hand some interview were made to the medical and nursing staff. The diagnosis allowed to verify the need of the research with social approach. The paper highlight how to incorporate patients from the primary health level, in order this program has a higher scope and the importance of the family support and the professional relationship to accomplish the quality required.