Background/Objectives: Brucella is a major global One Health threat, causing an estimated 2.1 million human infections and substantial livestock losses annually, with no vaccine currently available for humans, underscoring the urgent need for a safe and effective vaccine. Methods: Employing a reverse vaccinology approach, a novel 175-mer multiepitope vaccine (Mvax) targeting Brucella FrpB was computationally designed in this study, incorporating two B-cell, two MHC class I (MHC-I), and three MHC class II (MHC-II) epitopes selected for their high predicted antigenicity, safety, and IFN-γ-inducing potential. Human β-defensin-3 (hBD3) was fused to the N-terminus as an adjuvant, followed by comprehensive in silico evaluation of the construct. Results: Population coverage analysis predicted 99.59% global MHC class I/II coverage for selected epitopes. In silico analyses predicted that Mvax has high solubility (Protein-SOL score: 0.808), a high antigenicity score (VaxiJen: 1.06), and a negative GRAVY index (−0.881), indicating favorable predicted physicochemical characteristics. iMODS, CABS-Flex 3, and molecular dynamics simulations suggested theoretical stability trends for the modeled vaccine complexes. C-ImmSim immune simulations further predicted elevated Th1 cell populations and associated cytokines (IL-12, IFN-γ, IL-2) following both single and multiple simulated Mvax exposures. Conclusions: The computational analyses described here provide a theoretical modeling basis for an antivirulence multi-epitope vaccine design against human brucellosis, with predicted metrics and simulated immune responses requiring empirical validation.

Extracellular matrix (ECM) bioscaffolds have demonstrated therapeutic potential across a variety of clinical and preclinical applications for tissue repair and regeneration. In parallel, these scaffolds and their components have shown the capacity to modulate the immune response. Unlike synthetic implants, which are often associated with chronic inflammation or fibrotic encapsulation, ECM bioscaffolds interact dynamically with host cells, promoting constructive tissue remodeling. This effect is largely attributed to the preservation of structural and biochemical cues—such as degradation products and matrix-bound nanovesicles (MBV). These cues influence immune cell behavior and support the transition from inflammation to resolution and functional tissue regeneration. However, the immunomodulatory properties of ECM bioscaffolds are dependent on the source tissue and, critically, on the methods used for decellularization. Inadequate removal of cellular components or the presence of residual chemicals can shift the host response towards a pro-inflammatory, non-constructive phenotype, ultimately compromising therapeutic outcomes. This review synthesizes current basic concepts on the innate immune response to ECM bioscaffolds, with particular attention to the inflammatory, proliferative, and remodeling phases following implantation. We explore how specific ECM features shape these responses and distinguish between pro-remodeling and pro-inflammatory outcomes. Additionally, we examine the impact of manufacturing practices and quality control on the preservation of ECM bioactivity. These insights challenge the conventional classification of ECM bioscaffolds as medical devices and support their recognition as biologically active materials with distinct immunoregulatory potential. A deeper understanding of these properties is critical for optimizing clinical applications and guiding the development of updated regulatory frameworks in regenerative medicine.

Background/Objectives: Research efforts and substantial funding have been dedicated to finding cost-effective and sustainable alternatives to antibiotics. Probiotics have been proposed as promising substitutes for antibiotics in human nutrition and livestock production; however, their functional mechanisms remain incompletely understood, limiting their sustainable applications as food supplements, feed additives and for therapeutic and cosmetic purposes. Methods: In this study, the probiotic potential of two bacterial genomes, Ligilactobacillus saerimneri and Ligilactobacillus salivarius, were explored. Their protein-coding hypothetical proteins were analyzed for their potential to induce interleukin-5 (IL-5) and interleukin-13 (IL-13). Results: The IL-5- and IL-13-inducing peptides were identified as immunogens against bacterial and tumor peptides. Conclusions: These findings provide insights into the probiotic bacteria’s immune functionality pathways, sustainability and potential as therapeutic feed additives, food supplements and candidates for vaccine development.

Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on 20 July 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and October 2024, Wezlana® (Amgen ABP 654), Uzpruvo® (Alvotech AVT04) and Pyzchiva® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma® (Celltrion Healthcare CT-P43) was approved by the EMA in August 2024. Otulfi® (Fresenius Kabi/Formycon) was approved by the FDA in October 2024. Several other potential biosimilar candidates are under development, including BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g., Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review summarizes the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs.

Extracellular vesicles (EVs) encompass a diverse array of cell-derived vesicles, originating either from the endosomal compartment (exosomes) or generated through shedding from the cell membrane. These lipid bilayer nanovesicles carry a diverse cargo consisting of nucleic acids, various macromolecules, and growth factors, capable of being assimilated by nearby or distant cells through biofluids, thereby triggering a wide range of cellular responses. Given their distinctive biological characteristics and crucial roles in intercellular communication, EVs have garnered significant attention, especially concerning potential clinical applications. Inheriting cargo from their parent cells, EVs present promising resources for diverse disease biomarkers. Research elucidating the specific impacts of cargo on target cells has sparked enthusiasm for their therapeutic potential. Compelling evidence indicates that RNA cargo housed within EVs can modulate gene expression and influence cellular functions in recipient cells. However, despite significant progress, numerous aspects of EV biology remain obscure, encompassing selective cargo-loading mechanisms that yield distinct compositions from source cells, variability in size and content, and undisclosed pathways governing uptake and cargo fate in recipient cells. A thorough understanding of core EV mechanisms—such as generation, trafficking, and payload delivery—is essential for their effective clinical utilization. This review explores the current understanding of RNA loading and transportation within EVs, shedding light on the advancements made toward clinical applications.

The SARS-CoV-2 virus has caused a catastrophic impact on the world for the past 3 years. The virus has now returned with the emergence of the Omicron (B.1.1.529) variant. Within two months of its first emergence in South Africa, Omicron became the most dominating SARS-CoV-2 variant around the world, being the cause of the majority of new infections at present. Omicron has presented with the greatest transmission rate of all the previous variants despite the presence of mass vaccinations and acquired immunity. Several monoclonal antibodies and mRNA vaccines have failed to produce desired effects owing to a large number of mutations present in the Omicron variant. The introduction of the booster dose of the present mRNA vaccines has proven to be a great addition to the therapeutic armamentarium against the Omicron variant. Immunocompromised patients including the elderly, cancer patients, organ transplant recipients, and those with multiple comorbidities have been at a greater risk of developing severe diseases since the pre-Omicron era. The emergence of Omicron again raised a threat against this population. The protection from severe disease and mortality rates through the utilization of multiple immunizations and monoclonal antibodies has been controversial in this subgroup of patients. Thus, designing large-scale studies to evaluate the effectiveness of monoclonal antibodies and vaccines in these patients can provide evidence-based recommendations to improve survival in this population. This article attempts to discuss the different subvariants of Omicron, differences in the mutational aspects along with the particular focus on the consequences of the Omicron infection in the elderly population with diverse comorbidities.

Alzheimer’s disease (AD) is a neuropathology characterized by progressive cognitive impairment and dementia. The disease is attributed to senile plaques, which are aggregates of amyloid beta (Aβ) outside nerve cells; neurofibrillary tangles, which are filamentous accumulations of phosphorylated tau in nerve cells; and loss of neurons in the brain tissue. Immunization of an AD mouse model with Aβ-eliminated pre-existing senile plaque amyloids and prevented new accumulation. Furthermore, its effect showed that cognitive function can be improved by passive immunity without side effects, such as lymphocyte infiltration in AD model mice treated with vaccine therapy, indicating the possibility of vaccine therapy for AD. Further, considering the possibility of side effects due to direct administration of Aβ, the practical use of the safe oral vaccine, which expressed Aβ in plants, is expected. Indeed, administration of this oral vaccine to Alzheimer’s model mice reduced Aβ accumulation in the brain. Moreover, almost no expression of inflammatory IgG was observed. Therefore, vaccination prior to Aβ accumulation or at an early stage of accumulation may prevent Aβ from causing AD.

Flaviviruses, such as dengue, zika, yellow fever, West Nile, and Japanese encephalitis virus, are RNA viruses belonging to the Flaviviridae family (genus Flavivirus). They represent an important global health concern, since most areas of the world are endemic for at least one of these viruses. Although vaccines for five flaviviruses currently exist, there is a need for new vaccines to protect from established, emerging, and reemerging flaviviruses. Yellow fever vaccine shortages experienced in the last decade, combined with the risk of YFV spread to Asia and the restrictions of vaccine administration to certain population segments, show that even when a highly efficacious vaccine is available, new and improved vaccines might be needed. Virus-like particles (VLPs) are multiprotein structures that mimic the virus, but do not contain its genetic material. As such, VLPs have an excellent track record of strong immunogenicity and high safety, dating back to the introduction of the first recombinant hepatitis B vaccine in the 1980s. Flavivirus-like particles (FVLPs) have been extensively studied, especially for DENV, JEV, and ZIKV, and could give rise to next-generation recombinant subunit flavivirus vaccines based on VLPs incorporating molecular features intended to ensure high efficacy and minimize the risk of antibody-dependent enhancement (ADE) upon infection with other flaviviruses.

Patients with an immunocompromised state are at risk of developing a long-term infection from the coronavirus 2 that causes severe acute respiratory syndrome (SARS-CoV-2) [...]

The ongoing pandemic situation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global threat to both the world economy and public health. Therefore, there is an urgent need to discover effective vaccines or drugs to fight against this virus. The flavonoids and their medicinal plant sources have already exhibited various biological effects, including antiviral, anti-inflammatory, antioxidant, etc. This study was designed to evaluate different flavonoids from medicinal plants as potential inhibitors against the spike protein (Sp) and main protease (Mpro) of SARS-CoV-2 using various computational approaches such as molecular docking, molecular dynamics. The binding affinity and inhibitory effects of all studied flavonoids were discussed and compared with some antiviral drugs that are currently being used in COVID-19 treatment namely favipiravir, lopinavir, and hydroxychloroquine, respectively. Among all studies flavonoids and proposed antiviral drugs, luteolin and mundulinol exhibited the highest binding affinity toward Mpro and Sp. Drug-likeness and ADMET studies revealed that the chosen flavonoids are safe and non-toxic. One hundred ns-MD simulations were implemented for luteolin-Mpro, mundulinol-Mpro, luteolin-Sp, and mundulinol-Sp complexes and the results revealed strong stability of these flavonoid-protein complexes. Furthermore, MM/PBSA confirms the stability of luteolin and mundulinol interactions within the active sites of this protein. In conclusion, our findings reveal that the promising activity of luteolin and mundulinol as inhibitors against COVID-19 via inhibiting the spike protein and major protease of SARS CoV-2, and we urge further research to achieve the clinical significance of our proposed molecular-based efficacy.