Next-generation Dengue Vaccines: Leveraging Peptide-Based Immunogens and Advanced Nanoparticles as Delivery Platforms.

Dengue, caused by the dengue virus (DENV), is a prevalent arthropod-borne disease in humans and poses a significant burden on public health. Severe cases of dengue can be life-threatening. Although a licensed dengue vaccine is available, its efficacy varies across different virus serotypes and may exacerbate the disease in some seronegative recipients. Developing a safe and effective vaccine against all DENV serotypes remains challenging and requires continued research. Conventional approaches in dengue vaccine development, using live or attenuated microorganisms or parts of them often contain unnecessary epitopes, risking allergenic or autoimmune reactions. To address these challenges, innovative strategies such as peptide vaccines have been explored. Peptide vaccines offer a safer alternative by inducing specific immune responses with minimal immunogenic fragments. Chemical modification strategies of peptides have revolutionized their design, allowing for the incorporation of multi-epitope presentation, self-adjuvanting features, and self-assembling properties. These modifications enhance the antigenicity of the peptides, leading to improved vaccine efficacy. This review outlines advancements in peptide-based dengue vaccine development, leveraging nanoparticles as antigen-displaying platforms. Additionally, key immunological considerations for enhancing efficacy and safety against DENV infection have been addressed, providing insight into the next-generation of dengue vaccine development leveraging on peptide-nanoparticle technology.

New modular platform based on multi-adjuvanted amphiphilic chitosan nanoparticles for efficient lipopeptide vaccine delivery against group A streptococcus.

An effective vaccine against group A streptococcus (GAS) is highly desirable for definitive control of GAS infections. In the present study, two variants of amphiphilic chitosan nanoparticles-based GAS vaccines were developed. The vaccines were primarily composed of encapsulated KLH protein (a source of T helper cell epitopes) and lipidated M-protein derived B cell peptide epitope (lipoJ14) within the amphiphilic structure of nanoparticles. The only difference between them was one of the nanoparticles vaccines received additional surface coating with poly (I:C). The formulated vaccines exhibited nanosized particles within the range of 220-240 nm. Cellular uptake study showed that nanoparticles vaccine without additional poly (I:C) coating has greater uptake by dendritic cells and macrophages compared to nanoparticles vaccine that was functionalized with poly (I:C). Both vaccines were found to be safe in mice and showed negligible cytotoxicity against HEK293 cells. Upon immunization in mice, both nanoparticle vaccines produced high antigen-specific antibodies titres that were regulated by a balanced Th1 and Th2 response compared to physical mixture. These antibodies elicited high opsonic activity against the tested GAS strains. Overall, our data demonstrated that amphiphilic chitosan nanoparticles platform induced a potent immune response even without additional inclusion of poly (I:C).

Impact of Cognitive Dysfunction in the Middle East Depressed Patients: The ICMED Study.

BACKGROUND: Major depressive disorder is a common condition with a high rate of recurrence, chronicity, and affecting economic burden, including disability in the workplace, which leads to negative consequences on both individuals and society. OBJECTIVES: This study aimed to estimate the impact of cognitive dysfunction, as declared by the patient, on performing daily tasks/activities among patients with major depression disorder (MDD). METHODS: This investigation is based on multinational cross-sectional survey of 499 workers recruited from the Kingdom of Saudi Arabia (KSA) and United Arab Emirates (UAE). We assessed the severity of depression by Hamilton Depression Rating Scale (HDRS). Impact of Depression in the Workplace in Europe Audit (IDEA) survey and trial making test (TMT) parts A and B were used to assess the impact of cognitive dysfunction on performing daily tasks/activities in adult patients presented with MDD. RESULTS: A total of 499 persons were included in this study, aged 18-66 years, current workers and managers. Of them, 17.8% were normal (remitted), 22.4% were mildly depressed, 23.4% were moderately depressed, 8.6% were severely depressed, and 27.7% were very severely depressed at the time of the study according to HDRS. Common symptoms attributable to depression were low mode or sadness (89.8%), followed by insomnia (75.2%) and crying (70.9%). Of them, low mode or sadness was the most common factor affecting the work performance (90.2%). About 66.3% of participants diagnosed with depression by a doctor/medical professional. Awareness of the disease was recognizable by patients' managers in only 31.9% of the cases. Furthermore, 45.3% of cases had taken off work due to depression with mean duration of 38.7 (95% CI 37.7 to 39.7) days. The mean TMT parts A and B score were 69.2 (95% CI 66.3 to 72.2) and 126.6 (95% CI 121 to 132), respectively. Lastly, a significant positive correlation between the mean score for HDRS and TMT-A and B scores was observed. CONCLUSION: Depression affects work productivity and work environment with negative consequences to countries' economy. Awareness of depression in the workplace in KSA and UAE is still suboptimal. The personal and societal burden of this issue cannot be neglected when we become aware of the proportion of affected people.