ABSTRACT
BACKGROUND: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. METHODS AND RESULTS: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac. In vivo studies confirmed that fusion with mHla significantly augmented the immunogenicity of EpiVac, and it elicited both humoral and cellular immune responses in mice, which could be further enhanced by formulation with aluminum adjuvant. Furthermore, immunization with mHla-EpiVac demonstrated enhanced protective efficacy against K. pneumoniae channeling compared to EpiVac alone, resulting in reduced bacterial burden, secretion of inflammatory factors, histopathology and lung injury. Moreover, mHla fusion facilitated antigen uptake by mouse bone marrow-derived cells (BMDCs) and provided sustained activation of these cells. CONCLUSIONS: These findings suggest that mHla-EpiVac is a promising vaccine candidate against K. pneumoniae, and further validate the potential of mHla as a versatile carrier protein and adjuvant for antigen design.
Subject(s)
Bacterial Vaccines , Epitopes , Klebsiella Infections , Klebsiella pneumoniae , Animals , Klebsiella pneumoniae/immunology , Klebsiella Infections/prevention & control , Klebsiella Infections/immunology , Klebsiella Infections/microbiology , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage , Mice , Female , Epitopes/immunology , Mice, Inbred BALB C , Antigens, Bacterial/immunology , Lung/microbiology , Lung/immunology , Lung/pathology , Immunity, Cellular/drug effects , Staphylococcus aureus/immunology , Adjuvants, Immunologic/pharmacology , Immunity, Humoral/drug effectsABSTRACT
Incomplete optical distortion correction in VR HMDs leads to spatial dynamic distortion, which is a potential cause of VIMS. A perception experiment is designed for the investigation with three spatial distortion levels, with the subjective SSQ, five-scale VIMS level rating, and objective postural instability adopted as the evaluation metrics. The results show that the factor of spatial distortion level has a significant effect on all metrics increments (p<0.05). As the spatial distortion level drops off, the increments of VIMS symptoms decrease. The study highlights the importance of perfect spatial distortion correction in VR HMDs for eliminating the potential VIMS aggravation effect.
ABSTRACT
The awareness of self-position, which refers to the location of our cyclopean eye, is essential to the experience of being immersed and for interacting with a virtual environment. Currently, individual variability in the cyclopean eye location is not considered when presenting virtual reality (VR) content. The effect of the cyclopean eye shift was analyzed with theoretical and experimental methods, and it was found that human vision is sensitive to the visual direction offset caused by the cyclopean eye shift. To compensate for the cyclopean eye shift, an original model is proposed with shifting the 3D camera system accordingly. The proposed method is expected to make all individuals with different cyclopean eye shifts perceive the virtual environment from the same viewpoint as the designer desired and may achieve more accurate interaction.
