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Intro The concept of training immunity originally developed for other diseases has gained attraction during the epidemic. Several clinical trials and epidemiological analyses of populations previously immunized with BCG and other vaccines were the focus of scientific discussions. Here we show the activation of innate immunity markers both at mucosal and systemic levels with a mucosal vaccine CIGB2020 (HeberNasvacTM) containing virus-like particles (HBsAg) and nucleocapsid particle (HBcAg) of the hepatitis B virus. Moreover, the immune potentiating capacity of the HBcAg combined with RBD protein was used to formulate a specific mucosal vaccine candidate against SARS-CoV-2 (MambisaTM). Methods With CIGB 2020 (100µg HBsAg and 100 µg HBcAg) were conducted two proof of concept trials in human volunteers and a Phase I-II open, randomized, and controlled trial in 46 volunteers older than 60 years, symptomatic or close contact of COVID-19 patients. The volunteers were randomly assigned to the treatment group or not treated group. The nasal spray was administered to the treatment group on days 0, 7, and 14 together with daily sublingual administrations. Mucosal and serum samples were collected on days 0, 4, and 8. With MambisaTM vaccine (50µg RBD and 40 µg HBcAg) was conducted one proof of concept trial and a Phase I-II open and randomized trial in 1131 volunteers 19 to 60 years old, evaluating three different devices for nasal administration. All the volunteers gave written informed consent. Findings CIGB2020 activates interferon-induced genes and TLR 3, 7, and 8 at the level of oropharyngeal mucosa and PBMC. Monocyte and lymphocyte populations were also activated. One dose of the MambisaTM vaccine induces high levels of specific IgG. The serum and mucosal antibodies show RBD-ACE2 binding inhibition capacity and neutralization activity. Conclusion Nasal immunization exhibits advantages in inducing immunity at the level of the nasopharyngeal mucosa in addition to the systemic response.
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Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023
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Case report Background: Association of chronic spontaneous urticaria (CSU) with malignancies and worsening of urticaria during COVID-19 have been reported. The efficacy of treatment of CSU with omalizumab in the context of malignancies or COVID-19 is not well established. Method(s): Case report of a patient followed for 9 years with CSU. Data collected from Medical Records and interviews during consultations. Result(s): Female, 29 years-old, came to clinic in 2013 for investigation, diagnosed with CSU. She also presented mild asthma, allergic rhinitis and history of urticaria after taking amoxicillin. She had a positive autologous serum skin test, and positive skin tests to dust mite, cat, cockroach, peanut and milk. Her total IgE was 227IU/ mL. Anti-nuclear and anti-thyroid antibodies were negative;ERS 13mm, blood eosinophils 300/mm3, and stool exam negative for parasites. She showed no response to second generation antihistamines up to fourfold doses, with UCT < 6 and CU-QoL = 89. After 6 months, omalizumab was added at 300 mg subcutaneously, every 4 weeks. The patient showed immediate reactions after the two applications of omalizumab: first, diffuse pruritus and throat tightness;second, worsening of urticaria and pruritus, requiring iv medications. Treatment with omalizumab was stopped, she was kept on fourfold dose of bilastine with partial control of symptoms. In 2016, she presented worsening of urticaria (UCT = 1), weight loss of 6kg/2 months, daily fever and enlarged cervical lymph nodes, and was diagnosed with diffuse large B-cell non-Hodgkin's lymphoma. Following chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab, she presented complete resolution of urticaria. Two years after remission of the lymphoma, in 2019, she presented recurrence of urticaria, and treatment with fourfold dose of bilastine was reinitiated with control of symptoms (UCT = 16). Investigation ruled out recurrence of lymphoma. In May 2021, she was diagnosed with SARS-CoV- 2 infection. Symptoms of COVID-19 were runny nose and low grade fever, however urticaria got worse and no longer responsive to bilastine. Treatment with omalizumab was attempted, with no reactions and good efficacy after the first dose, with an UCT = 15, and urticaria remains controlled on treatment with omalizumab to present. Conclusion(s): In this report, we highlight the efficacy and safety of using omalizumab in a patient with refractory CSU associated with neoplasia and SARS-CoV- 2 infection.
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Introdução/Objetivo: Infecções Primárias da Corrente Sanguínea (IPCS) associam-se com elevada morbimortalidade em Unidades de Terapia Intensiva Neonatal (UTIN), e densidade de incidência (DI) de 17,3/1.000 cateter venoso central-dia (CVC-dia). Implementação de bundle de prevenção, através de modelo de melhoria, contribui para reduzir essas infecções. A pandemia COVID-19 exigiu dedicação integral dos profissionais, comprometendo o monitoramento das IPCS e adesão ao bundle de prevenção. O estudo visa determinar a variação na densidade de incidência de IPCS (DI-IPCS) em UTIN de Hospital Universitário de Pernambuco, após implementação de bundle para prevenção, entre abril de 2019 e agosto de 2021, aplicando o Modelo de Melhoria Breakthrough Series Collaborative method - Institute for Healthcare Improvement (BHS-IHI. Métodos: estudo quasi-experimental em UTIN comparando DI-IPCS-2018 (pré-intervenção) com dados 2019-2021 (período pós-intervenção) após implementação de bundle de prevenção (checklist inserção;checklist manutenção) para o CVC. Padronização diagnóstica IPCS, treinamentos para implementação dos bundles, reuniões semanais com ciclos PDSA (Plan-Do-Study-Act) e cálculos da DI, estratificada segundo o peso ao nascer, foram realizados. A variação na DI-IPCS foi analisada em três períodos: A (2018-2019);B (2019-2020) e C (2020-2021). Resultados: No período A, houve redução de DI-IPCS /1.000 CVC-dia para faixas de peso 751-1000g (DI = 28,2 para 7,3);1001-1500g (DI = 15,3 para 8,6);período B (COVID-19 em 2020) houve aumento na DI-IPCS para todas as faixas de peso, exceto RN > 2500g, a saber: < 750g (DI = 0 para 18,4);751-1.000g (DI = 7,3 para 22,92);1001-1500g (DI = 8,65 para 11,5;1501-2500g (DI = 11,8 para 19,0) e > 2500g (DI = 6,7 para 5,2). No período C, após reforço das medidas para prevenção, observou-se zero IPCS para as faixas de peso RN ao nascer < 750g e 1501-2500g e redução para 751-1.000g -DI = 15,87;1001-1500g -DI- = 5,71;> 2500g- DI-5,58. Taxa média de adesão ao bundle de inserção em 2019, 2020 e 2021 foram 75%, 74,3% e 75,3%, respectivamente;e taxa média de adesão 72% para bundle de manutenção (fevereiro, maio e agosto/2021) Conclusões: Obteve-se sucesso na redução de IPCS em UTIN com implementação de bundles para inserção/manutenção do CVC, através de ciclos de melhoria. Eventos de emergência em saúde pública representam um fator potencial para interrupção das boas práticas na assistência, exigindo planejamento de medidas para mitigar esta influência.