Adjuvant effects of interleukin-2 co-expression with VP60 in an oral vaccine delivered by attenuated Salmonella typhimurium against rabbit hemorrhagic disease
VETERINARY MICROBIOLOGY
Authors: Deng, Zhaobin; Geng, Yi; Wang, Kaiyu; Yu, Zehui; Yang, Ping Ou; Yang, Zexiao; He, Changliang; Huang, Chao; Yin, Lizi; He, Min; Tang, Li; Lai, Weimin
Abstract
Rabbit hemorrhagic disease (RHD) is a highly contagious infection that has caused significant damage to the rabbit industry since 1984. Inactivated vaccines, the currently used prevention measures, are effective in controlling RHD. However, these vaccines are derived from the livers of infected rabbits, which constitutes a major concern in terms of animal welfare and safety. Administration of DNA vaccines in collaboration with appropriate adjuvants, in particular, cytokines, to strengthen the immune response presents a novel optimization strategy to generate more efficient vaccines. In this study, the adjuvant effect of interleukin (IL)-2 co-expression with the VP60 gene in a DNA vaccine was evaluated. In total, four groups of 60 RHD virus (RHDV)-free rabbits (30 days old) were orally or subcutaneously administered recombinant SL7207-pVAX1-IL2-VP60, SL7207-pVAX1-VP60, SL7207-pVAX1 bacteria or the commercial inactive vaccine, and the induced immunity evaluated by challenge with the RHDV(Y8504/China) strain on day 56. The Recombinant SL7207-pVAX1-IL2-VP60 induced a higher level of antibodies than the vaccine SL7207-pVAX1-VP60 and inactivated vaccines to a significant extent. The concentrations of interleukin (IL)-4 were markedly higher than those in groups immunized with the naked or inactive vaccine alone. Furthermore, the fusion gene vaccine provided higher protection (93.33%) after virus challenge relative to immunization with the single gene (SL7207-pVAX1-VP60). The collective results indicate that recombinant SL7207-pVAX1-IL-2-VP60 bacteria exert enhanced protective effects against RHDV and therefore present a strong candidate as a potential vaccine. Moreover, IL-2 enhanced both humoral and cellular responses, highlighting the utility of rabbit IL-2 as an effective adjuvant.
Ex Vivo Exposure of Human Melanoma Tissue to Cold Physical Plasma Elicits Apoptosis and Modulates Inflammation
APPLIED SCIENCES-BASEL
Authors: Bekeschus, Sander; Moritz, Juliane; Helfrich, Iris; Boeckmann, Lars; Weltmann, Klaus-Dieter; Emmert, Steffen; Metelmann, Hans-Robert; Stoffels, Ingo; von Woedtke, Thomas
Abstract
Cutaneous melanoma is the most aggressive type of skin cancer with a not-sufficient clinical outcome. High tumor mutation rates often hamper a remedial treatment, creating the need for palliative care in many patients. To reduce pain and burden, local palliation often includes cryo-ablation, immunotherapy via injection of IL2, or electrochemotherapy. Yet, a fraction of patients and lesions do not respond to those therapies. To reach even these resistances in a redox-mediated way, we treated skin biopsies from human melanoma ex vivo with cold physical plasma (kINPen MED plasma jet). This partially ionized gas generates a potent mixture of reactive oxygen species (ROS). Physical plasmas have been shown to be potent antitumor agents in preclinical melanoma and clinical head and neck cancer research. The innovation of this technology lies in its ease-of-use without anesthesia, as the "cold" plasma temperature of the kINPen MED does not exceed 37 degrees C. In metastatic melanoma skin biopsies from six patients, we identified a marked increase of apoptosis with plasma treatment ex vivo. This had an impact on the chemokine/cytokine profile of the cultured biopsies, e.g., three of six patient-derived biopsy supernatants showed an apparent decrease in VEGF compared to non-plasma treated specimens. Moreover, the baseline release levels of 24 chemokines/cytokines investigated may serve as a useful tool for future research on melanoma skin biopsy treatments. Our findings suggest a clinically useful role of cold physical plasma therapy in palliation of cutaneous melanoma lesions, possibly in a combinatory setting with other immune therapies.