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1.
Article in English | MEDLINE | ID: mdl-38735888

ABSTRACT

Non-cholera Vibrio spp. includes ubiquitous organisms living in aquatic environments. Their occurrence is associated with global warming and meteorological disasters. In May 2023 the Romagna region, Italy, was affected by severe floods. In the following 15 weeks we observed 5 patients with invasive infections caused by V. vulnificus (3/5) and V. harveyi (2/5). All patients (median age 77 years) had medical comorbidities and shared exposure to seawater. Two patients needed surgery; 2 died. In conclusion, we observed an increased burden of Vibrio spp. invasive infections after May 2023 floods, affecting old patients with predisposing medical conditions.

2.
Am J Infect Control ; 52(1): 66-72, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37543306

ABSTRACT

PURPOSE: We describe the results of an infection control intervention, implemented in 4 tertiary hospitals in Romagna, Italy, aiming at containing the spread of carbapenem-resistant Enterobacterales (CRE). METHODS: The intervention consisted of rectal screening in patients at risk for CRE; pre-emptive contact precaution waiting for screening results; timely notification of CRE identification and concomitant computerized alert; contact precaution for confirmed CRE-positive patients. We performed an interrupted time series analysis to compare the incidence of CRE bacteraemia, of other CRE infections, and CRE-positive rectal swabs in the pre and postintervention period (January 2015-July 2017 and August 2017-June 2020, respectively). RESULTS: 4,332 CRE isolates were collected. Klebsiella pneumoniae was the most represented pathogen (n = 3,716, 85%); KPC production was the most common resistance mechanism (n = 3,896, 90%). The incidence rate of CRE bacteraemia significantly decreased from 0.554 to 0.447 episodes per 10.000 patient days in the early postintervention period (P = .001). The incidence rate of other CRE infections significantly decreased from 2.09 to 1.49 isolations per 10.000 patient days in the early postintervention period (P = .021). The monthly number of rectal swabs doubled in the postintervention period and there was a significant reduction trend of CRE-positive swabs, sustained over time (P < .001). CONCLUSIONS: The infection control intervention was successful in containing the spread of CRE infections and colonisations.


Subject(s)
Anti-Bacterial Agents , Bacteremia , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , beta-Lactamases , Bacterial Proteins , Trust , Infection Control/methods , Hospitals , Klebsiella pneumoniae , Bacteremia/epidemiology , Bacteremia/prevention & control , Bacteremia/drug therapy
3.
Ann Ig ; 35(4): 413-424, 2023.
Article in English | MEDLINE | ID: mdl-36255407

ABSTRACT

Background: During 2020, COVID-19 had a diversified distribution in Italy, the first nation in Europe to experience the outbreak of the epidemic. This was linked to geographical differences in population density and distribution of healthcare facilities, including Emergency Departments (EDs). This study aims to assess the impact of the pandemic on ED utilization in 2020 across different subpopulations and geographical locations in Italy. Methods: We used anonymized data from a survey conducted by the Italian National Institute of Statistics on 25,000 families to analyze the yearly rate of people who used EDs from 2015 to 2020. The rate of persons who accessed ED services in 2020 per 1,000 population was compared with those of the previous non-pandemic years. Results: The number of people accessing EDs in 2020 was 32.3% lower, although this reduction was not uniform across the 21 regions / autonomous provinces. People aged 0-14 years experienced the highest reduction in ED visits. In 2020, low educational level people exhibited a steeper reduction in the use of EDs. Conclusions: This study shows a significant drop in EDs use especially by children; the population section mostly affected by the effects of the pandemic. This study also confirms that education and socio-economic status are important determinants of ED use. The heterogeneous reduction in ED use across the regions of Italy highlights the need to further investigate the impact of this pattern on the health of the population, as well as to define adequate preparedness strategies to face future emergencies.


Subject(s)
COVID-19 , Child , Humans , COVID-19/epidemiology , Pandemics , Italy/epidemiology , Europe , Emergency Service, Hospital
4.
J Phys Condens Matter ; 34(26)2022 04 25.
Article in English | MEDLINE | ID: mdl-35390772

ABSTRACT

Ordered mesoporous silica (OMS) was proved to be an efficient oral adjuvant capable to deliver a wide in size variety of different antigens, promoting efficient immunogenicity. This material can be used in single or polivalent vaccines, which have been developed by a group of Brazilian scientists. The experiments performed with the model protein Bovine Serum Albumin (BSA) gave the first promissing results, that were also achieved by testing the virus like particle surface antigen of hepatitis B (HBsAg) and diphtheria anatoxin (dANA). Nanostructured OMS, SBA-15 type, with bi-dimensional hexagonal porous symmetry was used to encapsulate the antigens either in the mesoporous (pore diameter ∼ 10 nm) or macroporous (pore diameter > 50 nm) regions. This silica vehicle proved to be capable to create an inflammatory response, did not exhibit toxicity, being effective to induce immunity in high and low responder mice towards antibody production. The silica particles are in the range of micrometer size, leaving no trace in mice organs due to its easy expulsion by faeces. The methods of physics, usually employed to characterize the structure, composition and morphology of materials are of fundamental importance to develop proper oral vaccines in order to state the ideal antigen load to avoid clustering and to determine the rate of antigen release in different media mimicking body fluids.


Subject(s)
Silicon Dioxide , Vaccines , Adjuvants, Immunologic , Animals , Antigens , Hepatitis B Surface Antigens , Mice , Porosity , Silicon Dioxide/chemistry
5.
J Phys Condens Matter ; 34(24)2022 Apr 14.
Article in English | MEDLINE | ID: mdl-35344939

ABSTRACT

The Ca2MnReO6double perovskite is a spin-orbit-assisted Mott insulator with exotic magnetic properties, including a largely non-collinear Mn2+spin arrangement and nearly orthogonal coupling between such spins and the much smaller Re 5dmagnetic moments. Here, the electron-doped compound Ca1-xYxMnReO6(x= 0.1, 0.2 and 0.3) is reported and a detailed investigation is conducted forx= 0.3. Neutron and x-ray powder diffraction confirm that nearly full chemical order is maintained at the Mn and Re sites under the Y substitution at the Ca site. X-ray absorption measurements and an analysis of the Mn-O/Re-O bond distances show that the Mn oxidation state remains stable at +2 whereas Re is reduced upon doping. The electron doping increases the magnetic ordering temperature fromTc= 121 to 150 K and also enhances significantly the ferromagnetic component of the Mn spins at the expense of the antiferromagnetic component at the base temperature (T= 3 K). The lattice parameter anomalies atTcobserved in the parent compound are suppressed by the electron doping. The possible reasons for the enhanced magnetism and the suppressed magnetoelastic coupling in Ca1.7Y0.3MnReO6are discussed.

6.
Ann Ig ; 33(5): 456-473, 2021.
Article in English | MEDLINE | ID: mdl-34223864

ABSTRACT

Background: Perceived health is largely dependent on multiple socio-demographic and behavioral lifestyles and healthcare related factors. This could be accentuated when gender is taken into account. The aim of this study is to explore gender-related differences in multiple socio-demographic and behavioral lifestyles and healthcare related factors associated with individual health status and to identify those responsible for changes in perceived physical and mental health among men and women in Italy. Study design: We conducted a cross-sectional retrospective study to investigate the association between multiple socio-demographic and behavioral lifestyles and healthcare related factors and individual health status of 99,479 adults in Italy, using data and information obtained from a nationwide survey. Methods: To identify the factors that correlate with the perceived physical and mental health status between males and females, we employed a censored regression analysis, a Tobit model, stratifying the analysis by gender. Results: Socio-demographic and behavioral lifestyles factors differently impact on males and females and this impact is stronger on perceived physical than mental health. The perceived physical and mental health status resulted better for men than for women. The integrated analysis of gender differences in socio-demographic and behavioral lifestyles and determinants of health revealed important inequalities, mainly related to citizenship and educational level, among the socio-demographic factors, and smoking habit and obesity, among the behavioral lifestyle factors. Conclusions: Gender imbalances mainly fall into inequality in social inclusion, educational level, and healthy lifestyle. This demonstrates how gender differences are still abundantly present in the modern Italian society. Such information should be taken into consideration by policy makers when interventions to improve the health and quality of life of the population are planned or evaluated.


Subject(s)
Mental Health , Quality of Life , Adult , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Male , Retrospective Studies , Sex Factors , Socioeconomic Factors
7.
Sci Rep ; 11(1): 10934, 2021 05 25.
Article in English | MEDLINE | ID: mdl-34035366

ABSTRACT

Eating disorders (EDs) in patients with Parkinson's disease (PD) are mainly described through impulse control disorders but represent one end of the spectrum of food addiction (FA). Although not formally recognized by DSM-5, FA is well described in the literature on animal models and humans, but data on prevalence and risk factors compared with healthy controls (HCs) are lacking. We conducted a cross-sectional study including 200 patients with PD and 200 age- and gender-matched HCs. Characteristics including clinical data (features of PD/current medication) were collected. FA was rated using DSM-5 criteria and the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R). Patients with PD had more EDs compared to HCs (27.0% vs. 13.0%, respectively, p < 0.001). They mainly had FA (24.5% vs. 12.0%, p = 0.001) and night eating syndrome (7.0% vs. 2.5% p = 0.03). In PD patients, FA was associated with female gender (p = 0.04) and impulsivity (higher attentional non-planning factor) but not with the dose or class of dopaminergic therapy. Vigilance is necessary, especially for PD women and in patients with specific impulsive personality traits. Counterintuitively, agonist dopaminergic treatment should not be used as an indication for screening FA in patients with PD.


Subject(s)
Food Addiction/epidemiology , Night Eating Syndrome/epidemiology , Parkinson Disease/psychology , Aged , Case-Control Studies , Cross-Sectional Studies , Female , Food Addiction/etiology , Humans , Impulsive Behavior , Male , Middle Aged , Prevalence , Sex Characteristics
8.
Public Health ; 194: 182-184, 2021 May.
Article in English | MEDLINE | ID: mdl-33962094

ABSTRACT

OBJECTIVES: The objective of the study is to compare excess mortality (EM) patterns and spatial correlation between the first and second wave of the pandemic in Lombardy, the Italian region that paid an extremely high COVID-19-related mortality toll in March and April 2020. STUDY DESIGN: We conducted a longitudinal study using municipality-level mortality data. METHODS: We investigated the patterns and spatial correlation of EM of men aged ≥75 years during the first two pandemic waves (March-April 2020 vs November 2020) of COVID-19, using the mortality data released by the Italian National Institute of Statistics. EM was estimated at the municipality level to accurately detect the critical areas within the region. RESULTS: The areas that were mostly hit during the first wave of COVID-19 were generally spared by the second wave: EM of men aged ≥75 years in the municipality of Bergamo plummeted from +472% in March and April to -13% in November, and in Cremona the variation was from +344% to -19%. Conversely, in November 2020 EM was higher in some areas that had been protected in the first wave of the pandemic. Spatial correlation widely corroborates these findings, as large sections of the hot spots of EM detected in the first wave of the pandemic changed into cold spots in the second wave, and vice versa. CONCLUSIONS: Our results reveal the specular distribution of EM between the first and second wave of the pandemic, which may entail the consequences of social distancing measures and individual behaviors, local management strategies, 'harvesting' of the frailer population and, possibly, acquired immune protection. In conclusion, our findings support the need for continuous monitoring and analysis of mortality data using detailed spatial resolution.


Subject(s)
COVID-19/mortality , Pandemics , Aged , COVID-19/epidemiology , Cities/epidemiology , Humans , Italy/epidemiology , Longitudinal Studies , Male , Mortality/trends , Small-Area Analysis , Spatial Analysis
9.
Ig Sanita Pubbl ; 77(1): 381-403, 2021.
Article in Italian | MEDLINE | ID: mdl-33883749

ABSTRACT

The Covid-19 pandemic significantly increased the workload for the Italian Health Service. There is few information in the literature on the pediatric population and on the management of pediatric hospitals. The aim of this article is to describe the management of healthcare services during Covid-19 emergency in Regina Margherita Children's Hospital. The Regina Margherita Children's Hospital is specialized in the prevention, diagnosis and treatment of pediatric diseases. About 1000 health worker work in this Hospital and 278 hospitalization places are available.


Subject(s)
COVID-19 , Pandemics , Child , Emergency Service, Hospital , Hospitals, Pediatric , Humans , Italy , Public Health , SARS-CoV-2
10.
Ann Ig ; 33(1): 67-85, 2021.
Article in English | MEDLINE | ID: mdl-33354697

ABSTRACT

CONTEXT: Sedentary lifestyle is spreading among children living in urban settings. Recent studies in urban health investigated the effects of built environment on children's physical activity, focusing on the concept of "walkability", an index of how much an area is conducive to walking and active transportation. We decided to browse the literature in order to review all possible tools and methods by which walkability has been evaluated and measured. METHODS: We conducted a qualitative review of the literature in agreement with PRISMA guidelines, searching three medical databases for papers published between January 1994 and July 2017. Inclusion criteria were: primary studies, population ≤18 years and exposure variable as an assessment of walkability or built environment. RESULTS: We retrieved 1,702 articles and included 195 of them in the final review. Most of the studies were cross-sectional (n=188, 96.4%). We identified two possible approaches and four main tools to address walkability measurement. A subjective method approach was used in 71 studies (36.4%), an objective method in 87 (44.6%). Only 37 studies (19.0%) used both. Main tools were survey (n=70, 35.9%), Geographic Information System (GIS) (n=64, 32.8%), street audits (n=11, 5.6%) and Walk-score™ (n=3, 1.5%). Forty-six studies (23.4%) used mixed methods. Environmental variables' assessment and definition was found to vary greatly by method of choice. CONCLUSIONS: We found a high degree of heterogeneity regarding methods and measurements of walkability. A standard approach regarding tools and environmental variables' choice and definition will be advisable in order to allow comparisons among studies. Also, more longitudinal studies are needed.


Subject(s)
Environment Design , Residence Characteristics , Built Environment , Child , Cross-Sectional Studies , Humans , Walking
14.
Neuroophthalmology ; 44(2): 125-127, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32395163

ABSTRACT

Gilles de la Tourette syndrome (GTS) is a complex disorder characterized by the presence of motor and vocal tics, as well as neuropsychiatric pathological features. Visual field defects have also been described in GTS patients by Enoch et al. in the 1980s. In the current paper, the authors discuss Enoch et al. studies showing visual field defects in patients with GTS, presenting a similar case evaluated in the context of newer structural and functional examination modalities.

15.
Sleep Med ; 68: 190-198, 2020 04.
Article in English | MEDLINE | ID: mdl-32044557

ABSTRACT

OBJECTIVES/BACKGROUND: Rapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD. PATIENTS/METHODS: In sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years. RESULTS: At follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = -0.57,p = 0.04). CONCLUSION: Despite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.


Subject(s)
Parkinson Disease , REM Sleep Behavior Disorder , Aged , Humans , Levodopa , Middle Aged , Parkinson Disease/complications , Parkinson Disease/drug therapy , Polysomnography , REM Sleep Behavior Disorder/etiology , Sleep, REM
16.
Eur J Clin Microbiol Infect Dis ; 39(4): 749-751, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31858355

ABSTRACT

Community-acquired pneumonia (CAP) is one of the major causes of morbidity, mortality and hospitalization, and S. pneumoniae is the most frequently isolated etiologic agent. The pneumococcal urinary antigen test (PUAT) is among the recommended methods to identify the causative agent in CAP patients. A novel PUAT (IMMUNOCATCHTMStreptococcus pneumoniae) was compared with the Uni-GoldTMS. pneumoniae assay routinely used in our laboratory and with the widely used BinaxNOW® S. pneumoniae antigen card. A total of 218 (183 freshly harvested and 35 frozen) urine samples (US) submitted for the detection of pneumococcal urinary antigen (PUAT) between December 2016 and November 2018 were evaluated. A number of 160 negative and 41 positive concordant results were scored for all the three assays. A total of 17 US gave discrepant results. The sensitivity and specificity of Immunocatch compared with Uni-Gold were 73.2% and 98.8%, respectively, and compared with BinaxNOW were 97.6% and 98.8%, respectively. The overall percent agreement (OPA) and the Cohen's kappa coefficient between the Immunocatch and the Uni-Gold resulted 92.2% and 0.78%, respectively, and compared with BinaxNOW were 98.6% and 0.95%, respectively. These performances suggest that the novel Immunocatch S. pneumoniae test is a useful tool for qualitative detection of S. pneumoniae capsular antigen in US.


Subject(s)
Antigens, Bacterial/urine , Clinical Laboratory Techniques/standards , Pneumonia, Pneumococcal/diagnosis , Pneumonia, Pneumococcal/urine , Reagent Kits, Diagnostic/standards , Clinical Laboratory Techniques/methods , Community-Acquired Infections/diagnosis , Community-Acquired Infections/microbiology , Community-Acquired Infections/urine , Humans , Sensitivity and Specificity , Streptococcus pneumoniae
17.
Vaccine ; 37(43): 6415-6425, 2019 10 08.
Article in English | MEDLINE | ID: mdl-31519445

ABSTRACT

Hepatitis B virus causes acute and chronic infections in millions of people worldwide and, since 1982, a vaccine with 95% effectiveness has been available for immunization. The main component of the recombinant hepatitis B vaccine is the surface antigen protein (HBsAg). In this work, the effect of pH, ionic strength and temperature on the native state of the HBsAg antigen were studied by a combination of biophysical methods that included small angle X-ray scattering, synchrotron radiation circular dichroism, fluorescence and surface plasmon resonance spectroscopies, as well as in vivo and in vitro potency assays. The native conformation, morphology, radius of gyration, and antigenic properties of the HBsAg antigen demonstrate high stability to pH treatment, especially in the pH range employed in all stages of HBsAg vaccine production and storage. The HBsAg protein presents thermal melting point close to 56 °C, reaching a more unfolded state after crossing this point, but it only experiences loss of vaccine potency and antigenic properties at 100 °C. Interestingly, a 6-month storage period does not affect vaccine stability, and the results are similar when the protein is kept under refrigerated conditions or at room temperature (20 °C). At frozen temperatures, large aggregates (>200 nm) are formed and possibly cause loss of HBsAg content, but that does not affect the in vivo assay. Furthermore, HBsAg has a well-ordered secondary structure content that is not affected when the protein is formulated with silica SBA-15, targeting the oral delivery of the vaccine. The combined results from all the characterization techniques employed in this study showed the high stability of the antigen at different storage temperature and extreme values of pH. These findings are important for considering the delivery of HBsAg to the immune system via an oral vaccine.


Subject(s)
Hepatitis B Surface Antigens/chemistry , Hepatitis B Surface Antigens/immunology , Protein Stability , Temperature , Animals , Circular Dichroism , Female , Fluorescence , Hepatitis B Vaccines/chemistry , Hepatitis B Vaccines/immunology , Hepatitis B virus/chemistry , Hydrogen-Ion Concentration , Immunogenicity, Vaccine , Mice , Mice, Inbred BALB C , Protein Denaturation , Silicon Dioxide/chemistry , Surface Plasmon Resonance , Vaccine Potency
18.
BJOG ; 126(8): 984-995, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30786138

ABSTRACT

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.


Subject(s)
Body Mass Index , Gestational Weight Gain/physiology , Overweight/complications , Pregnancy Complications/etiology , Adult , Australia/epidemiology , Birth Weight , Cohort Studies , Europe/epidemiology , Female , Gestational Age , Humans , Infant, Newborn , North America/epidemiology , Odds Ratio , Pregnancy , Pregnancy Complications/epidemiology , Risk Factors
19.
Vaccine, v. 37, n. 43, p. 6415-6425, oct. 2019
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2868

ABSTRACT

Hepatitis B virus causes acute and chronic infections in millions of people worldwide and, since 1982, a vaccine with 95% effectiveness has been available for immunization. The main component of the recombinant hepatitis B vaccine is the surface antigen protein (HBsAg). In this work, the effect of pH, ionic strength and temperature on the native state of the HBsAg antigen were studied by a combination of biophysical methods that included small angle X-ray scattering, synchrotron radiation circular dichroism, fluorescence and surface plasmon resonance spectroscopies, as well as in vivo and in vitro potency assays. The native conformation, morphology, radius of gyration, and antigenic properties of the HBsAg antigen demonstrate high stability to pH treatment, especially in the pH range employed in all stages of HBsAg vaccine production and storage. The HBsAg protein presents thermal melting point close to 56°C, reaching a more unfolded state after crossing this point, but it only experiences loss of vaccine potency and antigenic properties at 100°C. Interestingly, a 6-month storage period does not affect vaccine stability, and the results are similar when the protein is kept under refrigerated conditions or at room temperature (20°C). At frozen temperatures, large aggregates (>200nm) are formed and possibly cause loss of HBsAg content, but that does not affect the in vivo assay. Furthermore, HBsAg has a well-ordered secondary structure content that is not affected when the protein is formulated with silica SBA-15, targeting the oral delivery of the vaccine. The combined results from all the characterization techniques employed in this study showed the high stability of the antigen at different storage temperature and extreme values of pH. These findings are important for considering the delivery of HBsAg to the immune system via an oral vaccine.

20.
Vaccine ; 37(43): 6415-6425, 2019.
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib17267

ABSTRACT

Hepatitis B virus causes acute and chronic infections in millions of people worldwide and, since 1982, a vaccine with 95% effectiveness has been available for immunization. The main component of the recombinant hepatitis B vaccine is the surface antigen protein (HBsAg). In this work, the effect of pH, ionic strength and temperature on the native state of the HBsAg antigen were studied by a combination of biophysical methods that included small angle X-ray scattering, synchrotron radiation circular dichroism, fluorescence and surface plasmon resonance spectroscopies, as well as in vivo and in vitro potency assays. The native conformation, morphology, radius of gyration, and antigenic properties of the HBsAg antigen demonstrate high stability to pH treatment, especially in the pH range employed in all stages of HBsAg vaccine production and storage. The HBsAg protein presents thermal melting point close to 56°C, reaching a more unfolded state after crossing this point, but it only experiences loss of vaccine potency and antigenic properties at 100°C. Interestingly, a 6-month storage period does not affect vaccine stability, and the results are similar when the protein is kept under refrigerated conditions or at room temperature (20°C). At frozen temperatures, large aggregates (>200nm) are formed and possibly cause loss of HBsAg content, but that does not affect the in vivo assay. Furthermore, HBsAg has a well-ordered secondary structure content that is not affected when the protein is formulated with silica SBA-15, targeting the oral delivery of the vaccine. The combined results from all the characterization techniques employed in this study showed the high stability of the antigen at different storage temperature and extreme values of pH. These findings are important for considering the delivery of HBsAg to the immune system via an oral vaccine.

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