VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants.

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology

Vaccines against Emerging and Neglected Infectious Diseases: An Overview.

Neglected Tropical Diseases (NTDs) are a group of diseases that are highly prevalent in tropical and subtropical regions, and closely associated with poverty and marginalized populations. Infectious diseases affect over 1.6 billion people annually, and vaccines are the best prophylactic tool against them. Along with NTDs, emerging and reemerging infectious diseases also threaten global public health, as they can unpredictably result in pandemics. The recent advances in vaccinology allowed the development and licensing of new vaccine platforms that can target and prevent these diseases. In this work, we discuss the advances in vaccinology and some of the difficulties found in the vaccine development pipeline for selected NTDs and emerging and reemerging infectious diseases, including HIV, Dengue, Ebola, Chagas disease, malaria, leishmaniasis, zika, and chikungunya

Sequential Change in T2* Values of Cartilage, Meniscus, and Subchondral Bone Marrow in a Rat Model of Knee Osteoarthritis

[[abstract]]Background: There is an emerging interest in using magnetic resonance imaging (MRI) T2* measurement for the evaluation of degenerative cartilage in osteoarthritis (OA). However, relatively few studies have addressed OA-related changes in adjacent knee structures. This study used MRI T2* measurement to investigate sequential changes in knee cartilage, meniscus, and subchondral bone marrow in a rat OA model induced by anterior cruciate ligament transection (ACLX). Materials and Methods: Eighteen male Sprague Dawley rats were randomly separated into three groups (n= 6 each group). Group 1 was the normal control group. Groups 2 and 3 received ACLX and sham-ACLX, respectively, of the right knee. T2* values were measured in the knee cartilage, the meniscus, and femoral subchondral bone marrow of all rats at 0, 4, 13, and 18 weeks after surgery. Results: Cartilage T2* values were significantly higher at 4, 13, and 18 weeks postoperatively in rats of the ACLX group than in rats of the control and sham groups (p,0.001). In the ACLX group (compared to the sham and control groups), T2* values increased significantly first in the posterior horn of the medial meniscus at 4 weeks (p= 0.001), then in the anterior horn of the medial meniscus at 13 weeks (p,0.001), and began to increase significantly in the femoral subchondral bone marrow at 13 weeks (p= 0.043). Conclusion: Quantitative MR T2* measurements of OA-related tissues are feasible. Sequential change in T2* over time in cartilage, meniscus, and subchondral bone marrow were documented. This information could be potentially useful for in vivo monitoring of disease progression.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[booktype]]電子版[[countrycodes]]US

Anterior crucial ligament rupture: self-healing through dynamic intraligamentary stabilization technique

PURPOSE: Surgery involving arthroscopic reconstruction of the injured ligament is the gold standard treatment for torn anterior cruciate ligament (ACL). Recent studies support the hypothesis of biological self-healing of ruptured ACL. The aim of the study is to evaluate, in an animal model, the efficacy of a new technique, dynamic intraligamentary stabilization that utilizes biological self-healing for repair of acute ACL ruptures. METHODS: The ACL in 11 adult female white alpine sheep was transected and in 8 sheep reconstructed by dynamic intraligamentary stabilization. To enhance the healing potential, microfracturing and collagen were used in all animals. The contralateral, non-operated knees served as controls. At 3 months postkilling, all animals were submitted to magnetic resonance imaging and biomechanical and histological evaluation. RESULTS: No surgery-related complications were observed. Postoperatively, all animals regularly used the operated leg with full weight bearing and no lameness. At the time of killing, all animals exhibited radiological and histological healing of the transacted ACL. Biomechanical tests confirmed successful restoration of anteroposterior translation in the dynamic intraligamentary stabilization knees. Histological examination revealed dense scar tissue at the ends of the transected ligaments exhibiting hypercellularity and hypervascularization. CONCLUSION: The dynamic intraligamentary stabilization technique successfully induced self-healing of ruptured ACL in a sheep model. Knee joints remained stable during the healing period allowing free range of motion and full weight bearing, and no signs of osteoarthritis or other intraarticular damage in the follow up were observed

Degeneration in ACL Injured Knees with and without Reconstruction in Relation to Muscle Size and Fat Content—Data from the Osteoarthritis Initiative

Anterior cruciate ligaments (ACL) injuries represent a major risk factor for early osteoarthritis (OA).To evaluate the prevalence and 4-year progression of knee OA measured with 3T MR-imaging in individuals with ruptured, reconstructed or normal ACL and to assess the impact of thigh muscle characteristics.A total of 54 knees (23/54 male, 31/54 female) were recruited from the Osteoarthritis Initiative (OAI). At baseline, 15/54 subjects had prevalent ACL ruptures and 15/54 subjects had prevalent ACL reconstruction (24/54 normal ACL). Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores, Physical Activity Scores of the Elderly (PASE) and thigh muscle characteristics including strength, fat infiltration (Goutallier score) and thigh muscle cross-sectional area (CSA) MR measurements were obtained at baseline. Whole-organ MR-imaging Scores (WORMS) were obtained at baseline and at a 4-year follow-up time-point. Multivariate regression models, adjusting for covariates (age, gender, body mass index), were used for statistical analysis.At baseline, subjects with prevalent ACL ruptures had worse WORMS total scores (mean±SEM, 44.1±3.5) than subjects with ACL reconstruction (30.8±4.0; P = 0.015) and worse than subjects with normal ACL (21.3±3.0; P<0.001). Cartilage scores were worse in both femorotibial compartments in ACL injured knees than in knees with normal ACL (P<0.05). Knees with ACL reconstruction showed an increased degeneration of the medial meniscus (P = 0.036), cartilage degeneration at the medial femoral condyle (P = 0.011). In a multivariate regression model, including both ACL groups and total muscle characteristics as influence parameters, high thigh muscle CSA, high muscle/ fat ratio and low Goutallier scores were associated with less degenerative changes at the knee, independent of ACL status. Knees with ACL reconstruction showed an increased progression of cartilage degeneration at the medial tibia compared to the normal ACL group (P = 0.027).High thigh muscle CSA is associated with less degenerative changes at the knee, independent of the ACL status and may potentially be advantageous in the prevention of early OA