Bacterial Membrane Vesicles as a Novel Vaccine Platform against SARS-CoV-2.

Throughout history, infectious diseases have plagued humanity, with outbreaks occurring regularly worldwide. Not every outbreak affects people globally; however, in the case of Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), it reached a pandemic level within a remarkably short period. Fortunately, advancements in medicine and biotechnology have facilitated swift responses to the disease, resulting in the development of therapeutics and vaccines. Nevertheless, the persistent spread of the virus and the emergence of new variants underscore the necessity for protective interventions, leading researchers to seek more effective vaccines. Despite the presence of various types of vaccines, including mRNA and inactivated vaccines against SARS-CoV-2, new platforms have been investigated since the pandemic, and research on bacterial membrane vesicles (BMVs) has demonstrated their potential as a novel COVID-19 vaccine platform. Researchers have explored different strategies for BMV-based COVID-19 vaccines, such as mixing the vesicles with antigenic components of the virus due to their adjuvant capacity or decorating the vesicles with the viral antigens to create adjuvanted delivery systems. These approaches have presented promising results in inducing robust immune responses, but obstacles such as reproducibility in obtaining and homogeneous characterization of BMVs remain in developing vesicle-based vaccines. Overall, the development of BMV-based vaccines represents a novel and promising strategy in the fight against COVID-19. Additional research and clinical trials are needed to further evaluate the potential of these vaccines to offer long-lasting protection against SARS-CoV-2 and its evolving variants.

Resting state functional connectivity in adolescent synthetic cannabinoid users with and without attention-deficit/hyperactivity disorder.

OBJECTIVE: Synthetic cannabinoids (SCs) have become increasingly popular in recent years, especially among adolescents. The first aim of the current study was to examine resting-state functional connectivity (rsFC) in SC users compared to controls. Our second aim was to examine the influence of comorbid attention-deficit/hyperactivity disorder (ADHD) symptomatology on rsFC changes in SC users compared to controls. METHODS: Resting-state functional magnetic resonance imaging (fMRI) analysis included 25 SC users (14 without ADHD and 11 with ADHD combined type) and 12 control subjects. RESULTS: We found (i) higher rsFC between the default mode network (DMN) and salience network, dorsal attention network and cingulo-opercular network, and (ii) lower rsFC within the DMN and between the DMN and visual network in SC users compared to controls. There were no significant differences between SC users with ADHD and controls, nor were there any significant differences between SC users with and without ADHD. CONCLUSIONS: We found the first evidence of abnormalities within and between resting state networks in adolescent SC users without ADHD. In contrast, SC users with ADHD showed no differences compared to controls. These results suggest that comorbidity of ADHD and substance dependence may show different rsFC alterations than substance use alone.

Microfluidic point-of-care testing for the detection of Bordetella pertussis: A mini-review.

Bordetella pertussis is a bacterial pathogen responsible for pertussis, which is a highly contagious respiratory disease. Despite the relatively high vaccination coverage, pertussis is considered a reemerging disease that necessitates enhanced strategies for identification, prevention, and control. The diagnosis of pertussis typically involves a combination of clinical evaluation, laboratory tests, and a thorough medical history. The current technologies for pertussis diagnosis have their own limitations, prompting the exploration of alternative diagnostic approaches that offer enhanced sensitivity, specificity, and speed. Microfluidic technology is considered a very promising tool for the diagnosis of infectious diseases, as it offers more rapid and accurate outputs. It allows point-of-care testing (POCT) at or near the patient site, which can be critical, especially for an outbreak or pandemic. In this paper, current pertussis diagnostic tools with their limitations were discussed, and microfluidic approaches for the diagnosis of pertussis were highlighted.

In silico analysis of virulence factors of Streptococcus uberis for a chimeric vaccine design.

Streptococcus uberis is one of the causative agents of bovine mastitis, which has detrimental effects on animal health and the dairy industry. Despite decades of research, the requirement for effective vaccines against the disease remains unmet. The goal of this study was to create a multi-epitope vaccine using five virulence factors of S. uberis through the reverse vaccinology approach, which has been employed due to its high efficiency and applicability. Plasminogen activator A (PauA), glyceraldehyde-3-phosphate dehydrogenase C (GapC), C5a peptidase, S. uberis adhesion molecule (SUAM), and sortase A (SrtA) were selected for the T cytotoxic (CTL) and B cell epitope analyses as they were extensively studied in S. uberis or other pathogens. Eighteen CTL and ten B cell epitopes that were antigenic, non-toxic, and non-allergenic were selected in order to design a chimeric vaccine candidate that in silico analysis revealed to be potentially immunogenic, non-allergenic, and stable. Molecular docking analysis of the vaccine candidate with Toll-like receptor (TLR) 2 and TLR 4 revealed stable interactions between the candidate and the immune receptors. Meanwhile, the stability of the docked complexes was confirmed using normal mode analysis. Additionally, in silico immune simulation of the vaccine candidate demonstrated the stimulation of primary immune responses, indicating that the chimeric protein can hold promise as a viable vaccine candidate for preventing S. uberis mastitis. Moreover, the current study can provide a background for designing epitope-based vaccines based on the explored epitopes.

Bordetella pertussis and outer membrane vesicles.

Bordetella pertussis is the causative agent of a respiratory infection called pertussis (whooping cough) that can be fatal in newborns and infants. The pathogen produces a variety of antigenic compounds which alone or simultaneously can damage various host cells. Despite the availability of pertussis vaccines and high vaccination coverage around the world, a resurgence of the disease has been observed in many countries. Reasons for the increase in pertussis cases may include increased awareness, improved diagnostic techniques, low vaccine efficacy, especially acellular vaccines, and waning immunity. Many efforts have been made to develop more effective strategies to fight against B. pertussis and one of the strategies is the use of outer membrane vesicles (OMVs) in vaccine formulations. OMVs are attracting great interest as vaccine platforms since they can carry immunogenic structures such as toxins and LPS. Many studies have been carried out with OMVs from different B. pertussis strains and they revealed promising results in the animal challenge and human preclinical model. However, the composition of OMVs differs in terms of isolation and purification methods, strains, culture, and stress conditions. Although the vesicles from B. pertussis represent an attractive pertussis vaccine candidate, further studies are needed to advance clinical research for next-generation pertussis vaccines. This review summarizes general information about pertussis, the history of vaccines against the disease, and the immune response to these vaccines, with a focus on OMVs. We discuss progress in developing an OMV-based pertussis vaccine platform and highlight successful applications as well as potential challenges and gaps.

Alterations of growth, biofilm-forming, and gene expression of Bordetella pertussis by antibiotics at sub-minimum inhibitory concentrations.

Bordetella pertussis is the primary agent of the acute respiratory disease pertussis. It has been reported that the disease has recently become more common, especially in adults and adolescents, and adaptation of the pathogen is thought to have an important influence on the recurrence of the disease. This study aims to determine the effect of erythromycin, azithromycin, and trimethoprim-sulfamethoxazole used in the treatment of pertussis on the virulence gene expressions (prn, ptxS1, fhaB), biofilm-forming and growth of B. pertussis. In this study, the minimum inhibitory concentration (MIC) values of azithromycin and erythromycin in B. pertussis local strain Saadet were determined to be 0.09 µg/mL and 0.3 µg/mL, respectively. However, the Tohama-I and Saadet strains were resistant to trimethoprim-sulfamethoxazole (MIC>32 µg/mL). The biofilm-forming of the Saadet strain decreased with the increase in antibiotic doses. It was observed that 1/32MIC erythromycin and 1/32MIC azithromycin upregulated the expression of fhaB in Tohama-I, whereas the expression of ptxS1 and prn significantly decreased in sub-MICs of erythromycin. In the Saadet strain, only ptxS1 was highly expressed at 1/16MIC azithromycin and erythromycin (p > 0.05). This is the first study to investigate the effect of sub-MIC antibiotics on the expression of virulence genes and biofilm-forming of B. pertussis.

Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach.

Blackleg is an infectious disease of animals that is commonly caused by Clostridium chauvoei and characterized by localized muscle necrosis. In this study, proteome-mining and immunoinformatics approaches were applied to identify novel antigenic proteins and to construct a multi-epitope vaccine against C. chauvoei. All proteins of C. chauvoei strains were retrieved from the NCBI Microbial Genome Database containing both genomic and proteomic data of prokaryotes. The proteins were analyzed to exclude non-redundant sequences and to determine antigenic, virulent, and non-allergenic vaccine candidates through several online tools, resulting in seven protein candidates. Cytotoxic T and B cell epitopes of these proteins were evaluated through the tools present in the immune epitope database and the prioritized antigenic epitopes were then conjugated via appropriate linkers to construct the vaccine candidate. After the evaluation of physicochemical properties of the construct, the tertiary structure was modeled and refined through trRosetta and GalaxyRefine, respectively. The quality of the 3D structure was validated by ERRAT score, z-score, and Ramachandran plot and the construct was then docked with bovine Toll-like receptor 4 (TLR 4) using ClusPro. The docked complex was subjected to Molecular Mechanics/Generalized Born Surface Area in the HawkDock server and normal mode analysis in the iMODS simulation suite to assess the binding energy and stability of the complex, respectively. Overall, the vaccine construct was found stable and energetically feasible for bovine TLR 4 binding. Therefore, it can be used as a multi-epitope vaccine construct in clostridial vaccines to control the blackleg disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s10989-021-10279-9.

Structural connectivity in adolescent synthetic cannabinoid users with and without ADHD.

Synthetic cannabinoids (SC) have become increasingly popular in the last few years, especially among adolescents. Given ADHD is overrepresented in patients with substance use across adolescents compared to the general population, the current study aims were two-fold: i) examine structural brain network topology in SC users compared to healthy controls and, ii) examine the influence of ADHD on network topology in SC users. Diffusion-weighted magnetic resonance imaging scans were acquired from 27 SC users (14 without ADHD and 13 with ADHD combined type) and 13 controls. Structural networks were examined using network-based statistic and connectomic analysis. We found that SC users without ADHD had significantly weaker connectivity compared to controls in bilateral hemispheres, most notably in edges connecting the left parietal and occipital regions. In contrast, SC users with ADHD showed stronger structural connectivity compared to controls. In addition, adolescent SC users with ADHD, but not without ADHD, displayed reduced network organization, indicated by lower clustering coefficient and modularity, suggesting that poor structural network segregation and preserved structural network integration. These results suggest that comorbidity of ADHD and substance dependence may show different structural connectivity alterations than substance use alone. Therefore, future connectivity studies in the substance use population should account for the presence of ADHD in their samples, which may be associated with disparate connectivity profiles.

Cortical Thickness and Subcortical Volumes in Adolescent Synthetic Cannabinoid Users with or Without ADHD: a Preliminary Study.

INTRODUCTION: Synthetic cannabinoids (SCs) have become increasingly popular in the last few years, especially among adolescents. Given Attention deficit/hyperactivity disorder (ADHD) is over represented in patients with substance use across adolescents compared to the general population, the current study aims were two-fold: i) examine cortical thickness, surface area and subcortical volumes in SC users compared to controls, ii) examine the influence of ADHD on cortical thickness, surface area and subcortical volumes in SC users. METHODS: Structural magnetic resonance imaging scans were acquired from 28 SC users (15 without ADHD and 13 with ADHD combined type) and 13 controls. RESULTS: We found that SC users both with and without ADHD groups have significantly reduced cortical thickness compared to controls in areas of the left caudal middle frontal and left superior frontal. In addition, SC users with ADHD also showed reduced cortical thickness in the right precentral and postcentral gyruses. We also found increased right nucleus accumbens volume in SC users without ADHD, but not with ADHD, compared to controls. CONCLUSION: These results suggest that similar to cannabis use, SC use has also negative effects on brain morphology and comorbidity of ADHD and substance dependence may show different cortical thickness and subcortical volume alterations than substance use alone.