Since 2022, mpox epidemics have been sustaining and escalating over the world, posing a significant public health challenge. While significant progress has been made in diagnostic methodologies, prophylactic vaccines, and therapeutic interventions to mitigate monkeypox virus (MPXV) infection, scientific understanding of MPXV and related orthopoxviruses continues to evolve progressively. In order to keep pace with recent advancements, herein we review progress in mpox research from five key perspectives. This article first summarizes the latest epidemiological profiles, incorporating different viral lineages globally and in China, while highlighting their evolutionary history and distinct clinical characteristics. The virological profiles of MPXV shed light on its complete infectious lifecycle and the formation of distinct virus particle types. Clinically approved classical detection methods and emerging novel testing techniques are provided, establishing a framework for early diagnosis of mpox patients. The efficacy and safety of both licensed vaccines and those under development are analyzed to underscore their value in preventing mpox infection. Additionally, progress in approved and newly identified potential therapeutic agents is summarized and discussed, aiming to provide insights for further drug development and clinical treatment strategies.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a notably poor response to therapy due to its immunosuppressive tumor microenvironment (TME) and intrinsic drug resistance. The oncolytic virus (OV) represents a promising therapeutic strategy capable of transforming the “cold” immunological profile of PDAC tumors to a “hot” one by reshaping the TME. 4-1BB (CD137), a crucial member of the tumor necrosis factor receptor superfamily, plays a significant role in T-cell activation and function. Methods: In this study, we constructed an oncolytic herpes simplex virus armed with 4-1BBL (oHSV-4-1BBL), the ligand for the 4-1BB receptor, and investigated its therapeutic effects in two mouse models of pancreatic cancer, Pan02_HVEM and KPC. Results: We found that oHSV-4-1BBL remarkably inhibited tumor growth and extended the median survival time in both models. To amplify the therapeutic effect, we further combined oHSV-4-1BBL with PD-1 antibody. This combination therapy not only further suppressed tumor growth but also extended the median survival time by an additional 11 days compared to oHSV (armed with GFP as a control) combined with PD-1 antibody treatment, with some mice achieving complete tumor regression. Conclusions: Our findings confirm the potential of combining oncolytic viral therapy with 4-1BB targeting in enhancing the treatment of pancreatic cancer.

Background/Objectives: Chemically or genetically detoxified pertussis toxin (PTx) is a crucial antigen component of the acellular pertussis vaccine. Chemical detoxification using glutaraldehyde generally causes significant structural changes to the toxin. However, how these structural changes in PTx affect its antigenic properties remains unclear. Additionally, there is limited knowledge regarding how many alterations in antigenic properties impact immunogenicity. Methods: To investigate the impact of structural changes on antigenic properties, we developed a sandwich ELISA to quantify the neutralizing epitopes on PTx. Subsequently, we analyzed different PTx toxoid (PTd) preparations with the assay. Additionally, we assessed the immunogenicity of various acellular pertussis vaccine candidates containing these PTd preparations. Finally, the assay was applied to evaluate the consistency of commercial batches of PTx and PTd intermediates. Results: The assay demonstrated reasonable specificity, accuracy, and precision, and it was sensitive enough to quantify variations in neutralizing epitopes among different PTd samples that shared the same protein concentration. Importantly, we found a positive correlation between the number of neutralizing epitopes in detoxified PTx and its immunogenicity, indicating that the amount of neutralizing epitopes present determines the immunogenicity of glutaraldehyde-inactivated PTx. Moreover, commercial batches of PTx and PTd intermediates exhibited minor variations in neutralizing epitopes. Conclusions: These findings have significant implications for developing acellular pertussis vaccines as they highlight the importance of preserving the neutralizing epitopes of PTx during detoxification to ensure the vaccine’s effectiveness. This assay is also valuable for the quality control of PTd as it more accurately represents the actual antigenic changes of PTx.

Chemically or genetically detoxified pertussis toxin (PTx) is a crucial antigen component of the acellular pertussis vaccine. Chemical detoxification using glutaraldehyde generally causes significant structural changes to the toxin. However, how these structural changes in PTx affect its antigenic properties remains unclear. Additionally, there is limited knowledge regarding how many alterations in antigenic properties impact immunogenicity. To investigate the impact of structural changes on antigenic properties, we developed a sandwich ELISA to quantify the neutralizing epitopes on PTx. Subsequently, we analyzed different PTx toxoid (PTd) preparations with the assay. Additionally, we assessed the immunogenicity of various acellular pertussis vaccine candidates containing these PTd preparations. Finally, the assay was applied to evaluate the consistency of commercial batches of PTx and PTd intermediates. The assay demonstrated reasonable specificity, accuracy, and precision, and it was sensitive enough to quantify variations in neutralizing epitopes among different PTd samples that shared the same protein concentration. Importantly, we found a positive correlation between the number of neutralizing epitopes in detoxified PTx and its immunogenicity, indicating that the amount of neutralizing epitopes present determines the immunogenicity of glutaraldehyde-inactivated PTx. Moreover, commercial batches of PTx and PTd intermediates exhibited minor variations in neutralizing epitopes. These findings have significant implications for developing acellular pertussis vaccines, as they highlight the importance of preserving the neutralizing epitopes of PTx during detoxification to ensure the vaccine's effectiveness. This assay is also valuable for the quality control of PTd, as it more accurately represents the actual antigenic changes of PTx.