Acontecimientos adversos en embarazadas con la vacuna tetravalente contra la gripe obtenida de cultivos celulares / Adverse events in pregnant women with the tetravalent influenza vaccine obtained from cell cultures

La vacunación de la gripe en embarazadas muestra una clara relación beneficio/riesgo. En la actualidad se están desarrollando vacunas contra la gripe utilizando nuevas plataformas. Es imprescindible analizar la seguridad de estas nuevas vacunas en este grupo poblacional, infrarrepresentado en los ensayos clínicos. En la temporada 2019-2020 se aconsejó una vacuna obtenida en cultivo celular a las embarazadas en 2comunidades autónomas. Se recogió información de los centros de vacunación y de farmacovigilancia de ambas comunidades. La tasa de notificación de casos de acontecimientos adversos tras la vacunación en embarazadas fue de 4,02/100.000 dosis administradas y, en mujeres de 18 a 64 años no embarazadas, de 5,9/100.000 dosis administradas. La tasa de acontecimientos adversos notificados fue de 8,04 y 17,74, respectivamente. No se notificaron abortos espontáneos, prematuridad ni malformaciones fetales. Este análisis señala la seguridad en embarazadas de la vacuna de la gripe obtenida de cultivos celulares.(AU)

Influenza vaccination in pregnant women shows a clear benefit/risk ratio. Influenza vaccines are currently being developed using new platforms. It is essential to analyze the safety of these new vaccines in this population group, underrepresented in clinical trials. In the 2019-2020 season, a vaccine obtained in cell culture was recommended to pregnant women in 2autonomous communities. Information is collected from the vaccination and pharmacovigilance centers of both communities. The reporting rate of adverse events after vaccination in pregnant women was 4.02/100,000 doses administered, and in non-pregnant women aged 18-64 years it was 5.9/100,000 doses administered. The rate of adverse events reported was 8.04 and 17.74, respectively. No spontaneous abortions, prematurity or fetal malformations were reported. This analysis suggests the safety in pregnant women of the influenza vaccine obtained from cell cultures.(AU)

Adverse events in pregnant women with the tetravalent influenza vaccine obtained from cell cultures.

Influenza vaccination in pregnant women shows a clear benefit/risk ratio. Influenza vaccines are currently being developed using new platforms. It is essential to analyse the safety of these new vaccines in this population group, underrepresented in clinical trials. In the 2019-2020 season, a vaccine obtained in cell culture was recommended to pregnant women in two autonomous communities. Information is collected from the vaccination and pharmacovigilance centres of both communities. The reporting rate of adverse events (AEs) after vaccination in pregnant women was 4.02/100,000 doses administered, and in non-pregnant women aged 18-64 years it was 5.9/100,000 doses administered. The rate of AE reported was 8.04 and 17.74 respectively. No spontaneous abortions, prematurity or foetal malformations were reported. This analysis suggests the safety in pregnant women of the influenza vaccine obtained from cell cultures.

Trends of Adverse Events Following Immunization (AEFI) Reports of Human Papillomavirus Vaccine in the Valencian Community-Spain (2008-2018).

Vaccine safety surveillance is essential in vaccination programs. We accomplished a descriptive study of surveillance AEFI-reporting rate in human papillomavirus (HPV) vaccine administered in the Valencian Community, Spain. Data were obtained from Spanish Pharmacovigilance Adverse Reactions Data (FEDRA). Reporting rates were calculated using local net doses distributed as the denominator. Trends were assessed using joinpoint regression with annual percent change (APC) reported. The AEFI-reports decreased between 2008 and 2018 in two periods, a fast decreasing rate from 2009 to 2011 (from 192.2 to 24.93 per 100000 doses; APC, -54.9%; 95%CI [-75.2; -17.7]), followed by a stable trend (-13% APC, 95%CI [-26.1; 2.4]). For the age group analysis, only the group aged 14-15 years old followed the same trend with -58.4% (95%CI [-73.9; -33.8]) APC during 2008-2011, and -8.8% (95%CI [-27.7; 15]) APC during 2011-2018. The majority of the reports (73.82%) were nonserious, involving reactions at or near the vaccination site, headache, and dizziness events. No death was reported. AEFI-reporting rates for HPV immunization in the Valencian Community have decreased considerably with two trend periods observed for girls aged 14-15 years old. Currently, the AEFI reporting rate shows a decreasing trend, perhaps following the Weber effect, and it could also be affected by media attention and coverage.

Targeted delivery of Cyclosporine A by polymeric nanocarriers improves the therapy of inflammatory bowel disease in a relevant mouse model.

The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects. As had already been demonstrated in previous studies, nano- to micrometer-sized drug particles will accumulate at inflamed mucosal areas, providing a platform for such purposes. CYA as incorporated in poly-(lactic-co-glycolic-Acid) (PLGA) nano- and mirocarriers, respectively, each homogeneous in size and providing controlled drug release over 24h at intestinal pH-value. For comparative reasons, a commercial formulation (Sandimmun Neoral®) was included in the study. In an acute model of DSS-induced inflammation in Balb/c mice, up to three doses were administered for each formulation: 50mg/kg, 25mg/kg and 12.5mg/kg. Drug-free particles were included as control. The following parameters were evaluated: body weight, colon length, colon weight/length ratio, cytokine expression and histological analysis. Plasma levels of CYA were analysed to compare systemic bioavailability. While disease parameters, such as, e.g. colon length, always improved with an optimum dose of 25mg/kg, the commercial and the microparticulate formulations led to measurable plasma levels and adverse effects in terms of body weight loss at the highest dose. In contrast, when administering the same doses as nanoparticles, plasma concentrations remained always below the detection limit, and the body weight of the animals remained unchanged. In conclusion, this study corroborates the potential of nanocarriers enabling an improved topical delivery of CYA to the inflamed gut mucosa after oral administration yielding the same improvement of disease parameters at only half the dose in comparison to microparticles and a commercial oral formulation, respectively, and at the same time minimizing systemic exposure and associated adverse effect.

Lipid Nanoparticles as Potential Gene Therapeutic Delivery Systems for Oral Administration.

BACKGROUND: Gene therapy has experimented an increasing attention in the last decades, due to its enormous potential applications in the medical field. It can be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides) to treat or prevent a disease state, generally a geneticbased one. APPLICATION: Other applications, like treating viral, bacterial or parasite infections or development of vaccines are gaining also interest. Efficient gene therapy is mainly dependent on the ability of the highly labile genetic material to reach the therapeutic target. For this purpose, different delivery systems have been designed and extensively investigated. Nanoparticles offer a broad range of possibilities in design, being prepared using biocompatible and biodegradable excipients, being therefore generally considered as safe. CONCLUSION: Oral delivery of the genetic material is also a great challenge, due to the complexity of this specific biological barrier. Special attention to all the intrinsic hazards for gene delivery due to the barrier must be taken into account during the particle design process. Particle design will also allow targeting to specific sites of the gastrointestinal tract. Solid lipid nanoparticles have been extensively studied in the oral drug delivery field, and also in gene delivery through other administration routes, but still not explored in oral gene delivery. In this manuscript, design considerations and particle-cell interaction mechanisms will be extensively reviewed, focusing on the oral route to encourage the scientific community to explore these valuable carriers for oral gene delivery.