Design and evaluation of a multi-epitope DNA vaccine against HPV16.

Cervical cancer, among the deadliest cancers affecting women globally, primarily arises from persistent infection with high-risk human papillomavirus (HPV). To effectively combat persistent infection and prevent the progression of precancerous lesions into malignancy, a therapeutic HPV vaccine is under development. This study utilized an immunoinformatics approach to predict epitopes of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) using the E6 and E7 oncoproteins of the HPV16 strain as target antigens. Subsequently, through meticulous selection of T-cell epitopes and other necessary elements, a multi-epitope vaccine was constructed, exhibiting good immunogenic, physicochemical, and structural characteristics. Furthermore, in silico simulations showed that the vaccine not only interacted well with toll-like receptors (TLR2/TLR3/TLR4), but also induced a strong innate and adaptive immune response characterized by elevated Th1-type cytokines, such as interferon-gamma (IFN-γ) and interleukin-2 (IL2). Additionally, our study investigated the effects of different immunization intervals on immune responses, aiming to optimize a time-efficient immunization program. In animal model experiments, the vaccine exhibited robust immunogenic, therapeutic, and prophylactic effects. Administered thrice, it consistently induced the expansion of specific CD4 and CD8 T cells, resulting in substantial cytokines release and increased proliferation of memory T cell subsets in splenic cells. Overall, our findings support the potential of this multi-epitope vaccine in combating HPV16 infection and signify its candidacy for future HPV vaccine development.

Through the stringent selection of T-cell epitopes and other necessary elements, a novel multi-epitope vaccine targeting HPV 16 E6 and E7 oncoproteins was constructed using an immunoinformatics approach.The vaccine designed can induce both cellular and humoral immune responses, encompassing all the required immunogenic, physicochemical, and structural characteristics for an ideal vaccine design. Moreover, it offers decent worldwide coverage.In animal studies, the vaccine demonstrated strong immune responses, including expansion of CD4 and CD8 T cells, cytokine release, and enhanced memory T cell proliferation, resulting in long-term anti-tumor effects, inhibition of tumor growth, and prolonged survival in tumor-bearing mice.The immunological evaluation of the designed vaccine suggests its potential as a novel vaccine candidate against HPV 16.

Vertical distribution of dissimilatory iron reducing communities in the sediments of Taihu Lake.

The reduction of Fe(III) coupled with the oxidation of organic matter, primarily stimulated by dissimilatory iron-reducing bacteria (DIRB) under anoxic conditions, is a critical biogeochemical process in lacustrine sediments. Many single strains have been recovered and investigated, however, the changes in the diversity of culturable DIRB communities with sedimentary depth have not been fully revealed. In this study, 41 DIRB strains affiliated to ten genera of phylum Firmicutes, Actinobacteria, and Proteobacteria were isolated from the sediments of Taihu Lake at three depths (0-2 cm, 9-12 cm, and 40-42 cm), referring to distinct nutrient conditions. Fermentative metabolisms were identified in nine genera (except genus Stenotrophomonas). The DIRB community diversity and the microbial iron reduction (MIR) patterns vary in vertical profiles. The community abundance varied with the TOC contents in vertical profiles. The DIRB communities, containing 17 strains of 8 genera, were most diverse in the surface sediments (0-2 cm), where organic matter was most abundant among the three depths. 11 DIRB strains of five genera were identified in the 9-12 cm sediments with the lowest content of organic matter, while 13 strains of seven genera were identified in deep sediments (40-42 cm). Among the isolated strains, phylum Firmicutes dominated the DIRB communities at three depths, while its relative abundance increased with depth. Fe2+ ion was recognized as the dominant microbial ferrihydrite-reducing product of DIRB from 0 to 12 cm sediments. Instead, lepidocrocite and magnetite were the main MIR products of DIRB retrieved from 40 to 42 cm. The results indicate that the MIR driven by fermentative DIRB is crucial in lacustrine sediments and that the distribution of nutrients and iron (minerals) likely influences the diversity of DIRB communities in the lacustrine sediments.