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Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline - an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their "dispositional endotype" at pre-vaccination baseline, could dictate response to vaccination.

The article in Cell Discovery discusses the role of human DDIT4L intron retention (DIR) in contributing to cognitive impairment and amyloid plaque formation in Alzheimer's disease (AD) patients. The study found that hypoxia induces aberrant splicing of DDIT4L, resulting in the production of DIR, which is elevated in AD patients and colocalizes with Aβ plaques in the brain. The research also highlights the potential of DIR as a therapeutic target for dementia, as inhibiting its function in mice alleviated cognitive decline. The study suggests that DIR may play a crucial role in Aβ deposition and plaque formation, making it a promising target for future therapies. [Extracted from the article]

Plant-derived nanovesicles (PDVs) as nanodrug delivery carriers have gained recognition due to their satisfactory biosafety. However, there remains a challenge to target tumor sites accurately due to the uncertain membrane protein components on the surface of vesicles. Herein, a composite nanodrug delivery system by encapsulating the chemotherapy drug DOX is establish to efficiently target breast cancer. The novel nanoplatform (LEVBD) is formed by embedding the membrane fragments from breast cancer cell with the lemon-derived nanovesicles (LEVs) as the foundational skeleton. LEVBD reveal wonderful homologous tumor targeting due to fusion of cancer cell membrane components with LEVs, and the encapsulation of hybrid vesicles facilitates the transcellular transport of drugs. After intravenous injection, LEVBD could efficiently and selectively home to homologous tumor sites even under competition from heterologous tumors and significantly inhibit tumor growth without any observable toxic side effects. The doping of homologous cancer cell membranes provides a paradigm for the precise delivery of drug delivery vehicles using plant-derived vesicles as the backbone. [ABSTRACT FROM AUTHOR]

Background/Objectives: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants worldwide. Maternal immunization to protect younger infants is supported by evidence that virus-neutralizing antibodies, which are efficiently transferred across the placenta from mother to fetus, are a primary immune mediator of protection. In maternal RSV vaccine studies, estimates of correlates of protection are elusive because many factors of maternal–fetal immunobiology and disease characteristics must be considered for the estimates. Methods: We developed statistical models that aims to predict vaccine efficacy (VE) in infants following maternal immunization by including quantifiable covariates of the antibody titer distribution of the mother (pre- and post-immunization), the transplacental transfer ratio of IgG antibodies, the rate of antibody decay, and RSV disease incidence rate, all of which are season- and time-dependent and vary by infant age. Result: Our model shows that integrating the lower respiratory tract disease risk based on infant airway diameter and associated airway resistance is critical to appropriately model predicted infant VE. The VE predictions by our models, which preceded maternal RSV prefusion F vaccine efficacy trial primary readouts, closely align with the VE outcomes of these field studies. Conclusion: Our models successfully predicted VE of the RSV maternal vaccines and have potential use in modeling the clinical trial out-comes of other respiratory disease vaccines where maternal antibodies play a role in the protection of newborns. [ABSTRACT FROM AUTHOR]

In video surveillance and intelligent traffic,bad weather such as foggy,rainy and snowy can seriously affect the visibility of video images.Therefore,it is very important to quickly identify the current weather conditions and make adaptive clearness processing of surveillance videos.Aiming at the problems of poor effect of traditional weather recognition methods and lack of weather image data sets,a multi-class weather image blocks data set is constructed,and a weather recognition algorithm based on image blocks and feature fusion is proposed.The algorithm uses traditional methods to extract four features,namely average gradient,contrast,saturation and dark channel,which are taken as the shallow features of weather images.The algorithm uses transfer learning to fine -tune the VGG16 pre-training model,and extracts the full-connection layer features of the fine-tuning model,which are taken as the deep features of the weather image.The shallow and deep features of weather images are fused and used as the final features to train the Softmax classifier.The classifier can realize the recognition of foggy,rainy,snowy and sunny wea-ther images. Experimental results show that the recognition accuracy of the proposed algorithm can reach 99.26%,and the algorithm can be used as a weather recognition module in the adaptive video image sharpening system.

Human cytomegalovirus (HCMV) is the most common congenital infection. Several HCMV vaccines are in development, but none have yet been approved. An understanding of the kinetics of CMV replication and transmission may inform the rational design of vaccines to prevent this infection. The salivary glands (SG) are an important site of sustained CMV replication following primary infection and during viral reactivation from latency. As such, the strength of the immune response in the SG likely influences viral dissemination within and between hosts. To study the relationship between the immune response and viral replication in the SG, and viral dissemination from the SG to other tissues, mice were infected with low doses of murine CMV (MCMV). Following intra-SG inoculation, we characterized the viral and immunological dynamics in the SG, blood, and spleen, and identified organ-specific immune correlates of protection. Using these data, we constructed compartmental mathematical models of MCMV infection. Model fitting to data and analysis indicate the importance of cellular immune responses in different organs and point to a threshold of infection within the SG necessary for the establishment and spread of infection. Author summary: Cytomegalovirus (CMV) is the most common congenital infection and causes an enormous burden of childhood disease. To gain insight into the immune requirements for controlling infection, we used a mouse model to reproduce characteristics of natural CMV infection, employing a low viral inoculum, and delivering the virus to the salivary glands (SG), a key site of CMV replication. Our results provide detailed data on the spatial and temporal spread of infection throughout the body and identify key immune correlates of the control of viral replication. By translating these findings into mechanistic mathematical models, we revealed the importance of organ-specific immune responses, particularly the requirement of TNF-α and IFN-γ to control infection within the salivary glands. Furthermore, our mathematical modeling allowed us to compare known characteristics of human CMV infection related to infection establishment and spread to those predicted in mice, underscoring the suitability of the MCMV model to study its human homologue. These insights provide guidance for developing targeted vaccines to prevent CMV infection and disease. [ABSTRACT FROM AUTHOR]

The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high‐throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune‐mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230. [ABSTRACT FROM AUTHOR]