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Jasset OJ, Lopez Zapana PA, Bahadir Z, Shook L, Dennis M, Gilbert E, Liu ZA, Yinger RV, Bald C, Bradford CG, Silfen AH, Klein SL, Pekosz A, Permar S, Konnikova L, Yonker LM, Lauffenburger D, Nelson A, Elovitz MA, Edlow AG
American journal of obstetrics and gynecology
2025-06-01
PMID: 39515450
Open the data in
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Immport Dataset Available
SDY2917
Adult
Antibodies, Viral
Female
Fetal Blood
Gestational Age
HIPC 3 (2022)
Humans
Immunity, Maternally-Acquired
Infant
Infant, Newborn
Male
Massachusetts Institute of technology
Maternal-Fetal Exchange
Placenta
Pregnancy
Pregnancy Complications, Infectious
Prospective Studies
Respiratory Syncytial Virus Infections
Respiratory Syncytial Virus, Human
Respiratory Syncytial Virus Vaccines
Time Factors
Vaccination
Abstract:
[{'@Label': 'BACKGROUND', '@NlmCategory': 'BACKGROUND', '#text': 'Respiratory syncytial virus is associated with significant neonatal and infant morbidity and mortality. Maternal bivalent respiratory syncytial virus prefusion F respiratory syncytial virus vaccination to protect neonates and infants was approved in September 2023 for administration between 32+0 and 36+6 weeks to protect neonates and infants. This approved timeframe is narrower than the 24 to 36 week window evaluated in the clinical trial, due to the possible association between preterm birth and vaccine administration. Currently, data are lacking on how maternal vaccine timing within the approved window affects the transfer of antibodies from mother to fetus, critical information that could influence clinical practice.'}, {'@Label': 'OBJECTIVE', '@NlmCategory': 'OBJECTIVE', '#text': 'We sought to examine how gestational age at vaccination and time elapsed from maternal respiratory syncytial virus vaccination to delivery impacted transfer of maternal antibodies measured in the umbilical cord at delivery and in peripheral blood of 2-month infants. We also examined differences in maternal and cord respiratory syncytial virus antibody levels achieved by vaccination vs natural RSV infection.'}, {'@Label': 'STUDY DESIGN', '@NlmCategory': 'METHODS', '#text': 'A prospective cohort study was conducted at 2 academic medical centers between September 20, 2023 and March 21, 2024, enrolling 124 individuals who received the respiratory syncytial virus vaccine during pregnancy. Infant capillary blood was collected at 2 months of age from 29 of the infants. Maternal and cord immunoglobulin G levels achieved by respiratory syncytial virus vaccination were compared to those associated with maternal natural respiratory syncytial virus infection, using banked blood from 20 maternal:cord dyads collected prior to the availability of the maternal respiratory syncytial virus vaccine. Levels of immunoglobulin G against respiratory syncytial virus strain A2 and B fusion (F) and attachment (G) proteins and against pertussis toxin (as a comparator antigen from a vaccine routinely administered earlier in pregnancy) were measured using a Binding Antibody Multiplex Assay. Differences in titers between vaccination and natural infection were examined using Wilcoxon rank-sum test. Differences in cord:maternal transfer ratios and 2-month infant antibody levels by timing of maternal vaccination were evaluated by Kruskal-Wallis testing.'}, {'@Label': 'RESULTS', '@NlmCategory': 'RESULTS', '#text': 'Maternal respiratory syncytial virus vaccination resulted in significantly higher maternal and cord antirespiratory syncytial virus F antibody levels than natural infection (5.72 vs 4.82 log10 mean fluorescence intensity, P<.0001 maternal; 5.81 vs 5.03 log10 mean fluorescence intensity, P<.0001 cord). Maternal vaccination 2 to 3 weeks and 3 to 4 weeks prior to delivery was associated with significantly lower cord:maternal transfer ratios than were observed when vaccination occurred >5 weeks prior to delivery (P=.03 for 2-3 weeks, P=.007 for 3-4 weeks), and significantly lower transfer ratios than observed for pertussis vaccination administered prior to 30 weeks of gestation (P=.008 for 2-3 weeks, P=.03 for 3-4 weeks, similar at >4 weeks).'}, {'@Label': 'CONCLUSION', '@NlmCategory': 'CONCLUSIONS', '#text': 'Vaccine administration earlier in the approved 32 to 36 week window (at least 5 weeks prior to delivery) results in the highest transplacental transfer of maternal antibodies to the neonate. These results should inform the counseling of pregnant individuals on optimal vaccination timing.'}]
Jones DC, Elz AE, Hadadianpour A, Ryu H, Glass DR, Newell EW
Nature methods
2025-05-22
PMID: 40404994
HIPC 2 (2015)
HIPC 3 (2022)
Seattle Children's Research Institute
Abstract:
Single-cell spatial transcriptomics promises a highly detailed view of a cell's transcriptional state and microenvironment, yet inaccurate cell segmentation can render these data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation, in a method called Proseg (probabilistic segmentation), to rapidly infer morphologically plausible cell boundaries. Benchmarking applied to datasets generated by three commercial platforms shows superior performance and computational efficiency of Proseg when compared to existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult-to-segment tumor-infiltrating immune cells such as neutrophils and T cells. Last, through improvements in our ability to delineate subsets of tumor-infiltrating T cells, we show that CXCL13-expressing CD8+ T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from samples from patients with renal cell carcinoma.
Bustos Carrillo FA, Ojeda S, Sanchez N, Plazaola M, Collado D, Miranda T, Saborio S, Lopez Mercado B, Carey Monterrey J, Arguello S, Campredon L, Chu Z, Carlson CJ, Gordon A, Balmaseda A, Kuan G, Harris E
medRxiv : the preprint server for health sciences
2025-05-17
PMID: 39830280
HIPC 2 (2015)
Abstract:
[{'@Label': 'BACKGROUND', '@NlmCategory': 'UNASSIGNED', '#text': 'Dengue, chikungunya, and Zika are diseases of major human concern. Differential diagnosis is complicated in children and adolescents by their overlapping clinical features (signs, symptoms, and complete blood count results). Few studies have directly compared the three diseases. We aimed to identify distinguishing pediatric characteristics of each disease.'}, {'@Label': 'METHODS', '@NlmCategory': 'UNASSIGNED', '#text': 'Data were derived from laboratory-confirmed cases (symptomatic infections) aged 2-<18 years enrolled in a longitudinal cohort study in Managua, Nicaragua, and attending a primary health care center from January 19, 2006, through December 31, 2023. We collected clinical records and laboratory results across the first 10 days of illness. Data were analyzed with generalized additive models, day-and-disease-specific prevalence estimates, and machine learning models.'}, {'@Label': 'FINDINGS', '@NlmCategory': 'UNASSIGNED', '#text': 'We characterized 1,405 dengue, 517 chikungunya, and 522 Zika pediatric cases. We included 1,165 (47·7%) males and 1,279 (52·3%) females, with a median age of 10·0 (IQR 7·0-12·7) years. The prevalence of many clinical features exhibited by dengue, chikungunya, and Zika cases differed substantially overall, by age, and by day of illness. Dengue cases were differentiated most by abdominal pain (Prevalence difference (PD) 19·1%, 95% confidence interval (CI): 15·7%, 22·9%), leukopenia (PD 41·1%, 95% CI: 36·2%, 45·6%), nausea (PD 15·5%, 95% CI: 12·2%, 19·2%), vomiting (PD 21·9%, 95% CI: 17·9%, 26·1%), and basophilia (PD 42·3%, 95% CI: 37·4%, 47·0%); chikungunya cases were differentiated most by arthralgia (PD 60·5%, 95% CI: 56·3%, 64·2%) and the absence of leukopenia (PD -32·0%, 95% CI: -36·7%, -27·1%) and papular rash (PD -14·9%, 95% CI: -17·2%, -12·7%); and Zika cases were differentiated most by rash (PD 31·8%, 95% CI: 27·0%, 36·2%) and the lack of fever (PD -37·3%, 95% CI: -41·7%, -33·0%) and lymphocytopenia (PD -41·9%, 95% CI: -46·6%, -37·1%). Dengue and chikungunya cases exhibited similar temperature dynamics during acute illness, and their temperatures were higher than Zika cases. Sixty-two laboratory-confirmed afebrile dengue cases, which would not be captured by any widely used international case definition, presented very similarly to afebrile Zika cases, though some exhibited warning signs of disease severity. The presence of arthralgia, the presence of basophilia, and the absence of fever were the most important model-based distinguishing predictors of chikungunya, dengue, and Zika, respectively.'}, {'@Label': 'INTERPRETATIONS', '@NlmCategory': 'UNASSIGNED', '#text': 'These findings substantially update our understanding of dengue, chikungunya, and Zika in children while identifying various clinical features that could improve differential diagnoses. The occurrence of afebrile dengue warrants reconsideration of current guidance.'}, {'@Label': 'FUNDING', '@NlmCategory': 'UNASSIGNED', '#text': 'US National Institutes of Health R01AI099631, P01AI106695, U01AI153416, U19AI118610.'}]
Davis-Porada J, Tozlu C, Aiello C, Apostolidis SA, Bar-Or A, Bove R, Espinoza DA, Ferreira Brito S, Jacobs D, Kakara M, Onomichi K, Ricci A, Sabatino JJ, Walker E, Wherry EJ, Zhang L, Zhu W, Xia Z, De Jager P, Wesley SF, Straus Farber R, Farber DL
NPJ vaccines
2025-05-17
PMID: 40382362
Columbia University
HIPC 2 (2015)
HIPC 3 (2022)
Abstract:
Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1-70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4+ and CD8+ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity.
Feng Y, de Jong SE, Oliveira APBN, Samaha H, Yang F, Hu M, Wang Y, Beydoun N, Xie X, Zhang H, Kazmin D, Fang Z, Zou J, Gewirtz AT, Boyd SD, Hagan T, Rouphael N, Pulendran B
Cell host & microbe
2025-05-14
PMID: 40252648
Anti-Bacterial Agents
Antibodies, Viral
Bile Acids and Salts
Female
Gastrointestinal Microbiome
HIPC 3 (2022)
Humans
Immunity, Humoral
Male
Rabies
Rabies Vaccines
Stanford
Th1 Cells
Vaccination
Abstract:
The gut microbiome plays a crucial role in modulating human immunity. Previously, we reported that antibiotic-induced microbiome perturbation affects influenza vaccine responses, depending on pre-existing immunity levels. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on both primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration reduced the gut bacterial load, with a long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced (1) an enhanced pro-inflammatory signature early after vaccination, (2) a shift in the balance of vaccine-specific T-helper 1 (Th1) to T-follicular-helper response toward Th1 phenotype, and (3) profound alterations in metabolites, particularly in secondary bile acids in the blood. By integrating multi-omics datasets, we generated a multiscale, multi-response network that revealed key regulatory nodes, including the microbiota, secondary bile acids, and humoral immunity to vaccination.
Haralambieva IH, Ratishvili T, Goergen KM, Grill DE, Simon WL, Chen J, Ovsyannikova IG, Poland GA, Kennedy RB
Vaccine
2025-05-10
PMID: 40127573
Adult
Antibodies, Neutralizing
Antibodies, Viral
B-Lymphocytes
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Female
Hemagglutination Inhibition Tests
HIPC 1 (2010)
Humans
Influenza, Human
Influenza Vaccines
Killer Cells, Natural
Lymphocytes
Male
MicroRNAs
Middle Aged
Vaccines, Inactivated
Young Adult
Abstract:
Alterations of gene expression by miRNAs contribute substantially to genetic regulation and cellular functions. We conducted a comprehensive study in 53 individuals before and after seasonal inactivated influenza vaccine to characterize lymphocyte-specific miRNA expression (in purified B cells, CD4+ T cells, CD8+ T cells, and NK cells) and its effect on influenza vaccine-induced immune outcomes (hemagglutination inhibition antibody titers/HAI, viral neutralizing antibody titers /VNA, and memory B cell ELISPOT). Overall, we observed relatively stable miRNA expression before and after influenza vaccination. Statistical analysis uncovered three baseline miRNAs (miR-150-3p, miR-629-5p, and miR-4443) that were significantly correlated with influenza vaccine-induced immune outcomes in different cell types. Predictive modeling of influenza vaccine-induced HAI/VNA titers identified a set of specific baseline miRNAs in CD4+ T cells as factors predictive of antibody responses. A pathway enrichment analysis on the putative target genes revealed several regulated signaling pathways and functions: TGF-β signaling, PI3K-Akt signaling, p53 signaling, MAPK signaling, TNF signaling, and C-type lectin receptor signaling, as well as cell adhesion and adherens junctions, and antiviral host response. In conclusion, our study offers evidence for the role of epigenetic modification (miRNAs) on influenza vaccine-induced immunity. After validation, identified miRNAs may serve as potential biomarkers of immune response after influenza vaccination.
Krammer F, Hermann E, Rasmussen AL
Journal of virology
2025-04-15
PMID: 40145745
Animals
Birds
Cattle
Disease Outbreaks
HIPC 3 (2022)
History, 20th Century
History, 21st Century
Humans
Icahn School of Medicine at Mount Sinai
Influenza A Virus, H5N1 Subtype
Influenza, Human
Influenza in Birds
Pandemics
Poultry
Viral Zoonoses
Zoonoses
Abstract:
The H5N1 avian panzootic has resulted in cross-species transmission to birds and mammals, causing outbreaks in wildlife, poultry, and US dairy cattle with a range of host-dependent pathogenic outcomes. Although no human-to-human transmission has been observed, the rising number of zoonotic human cases creates opportunities for adaptive mutation or reassortment. This Gem explores the history, evolution, virology, and epidemiology of clade 2.3.4.4b H5N1 relative to its pandemic potential. Pandemic risk reduction measures are urgently required.
Wan M, Simonin EM, Johnson MM, Zhang X, Lin X, Gao P, Patel CJ, Yousuf A, Snyder MP, Hong X, Wang X, Sampath V, Nadeau KC
EMBO molecular medicine
2025-04-01
PMID: 39870881
Environmental Exposure
Exposome
HIPC 3 (2022)
Humans
Molecular Medicine
Precision Medicine
Stanford
Abstract:
The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses. These molecular alterations can aid as biomarkers for the diagnosis, disease prediction, early detection, and treatment and offering new avenues for personalized medicine. Advances in high throughput omics and other technologies as well as increased computational analytics is enabling comprehensive measurement and sophisticated analysis of the exposome to elucidate their cumulative and combined impacts on health, which can enable individuals, communities, and policymakers to create programs, policies, and protections that promote healthier environments and people. This review provides an overview of the potential role of exposomics in molecular medicine, covering its history, methodologies, current research and applications, and future directions.
Hart TM, Cui Y, Telford SR, Marín-López A, Calloway K, Dai Y, Matias J, DePonte K, Jaycox J, DeBlasio M, Hoornstra D, Belperron AA, Cibichakravarthy B, Johnson EE, Alameh MG, Dwivedi G, Hovius JWR, Bockenstedt LK, Weissman D, Ring AM, Fikrig E
Science translational medicine
2025-03-26
PMID: 40138454
Animals
Antigens
Feeding Behavior
Female
Guinea Pigs
HIPC 1 (2010)
HIPC 2 (2015)
HIPC 3 (2022)
Humans
Immunoglobulin G
Ixodes
Lyme Disease
Mice
Proteome
Tick Bites
Vaccination
Yale University
Abstract:
Ixodes scapularis is a primary vector of tick-borne pathogens in North America. Repeated exposure to these ticks can induce a humoral response to tick antigens and acquired tick resistance. However, identifying antigens contributing to this resistance is challenging because of the vast number of I. scapularis proteins secreted during feeding. To address this, we developed I. scapularis rapid extracellular antigen monitoring (IscREAM), a technique to detect antibody responses to more than 3000 tick antigens. We validated IscREAM with immunoglobulin G (IgG) from guinea pigs vaccinated with tick antigens, including a cement antigen cocktail that induced tick resistance. Furthermore, we explored the natural response to tick bites by profiling antigens recognized by IgG isolated from a tick-resistant individual, as well as from others with Lyme disease and tick-bitten guinea pigs and mice, to identify 199 recognized antigens. We observed that several antigens contained histamine-binding domains. This work enhances our understanding of the host immune response to I. scapularis and defines immunogen candidates for future antitick vaccines.
Chen G, Mohsin A, Zheng H, Rosenberg-Hasson Y, Padilla C, Sarin KY, Dekker CL, Grant P, Maecker HT, Lu Y, Furman D, Shen-Orr S, Khatri P, Davis MM
Proceedings of the National Academy of Sciences of the United States of America
2025-03-25
PMID: 40117305
Adult
Aged
Aged, 80 and over
Age Factors
Aging
Cellular Senescence
Cytokines
Female
HIPC 1 (2010)
Humans
Longitudinal Studies
Male
Middle Aged
Neoplasms
Abstract:
Aging is associated with increased variability and dysregulation of the immune system. We performed a system-level analysis of serum cytokines in a longitudinal cohort of 133 healthy individuals over 9 y. We found that cancer incidence is a major contributor to increased cytokine abundance variability. Circulating cytokines increase up to 4 y before a cancer diagnosis in subjects with age over 80 y. We also analyzed cytokine expression in 10 types of early-stage cancers from The Cancer Genome Atlas. We found that a similar set of cytokines is upregulated in tumor tissues, specifically after the age of 80 y. Similarly, cellular senescence activity and CDKN1A/p21 expression increase with age in cancer tissues. Finally, we demonstrated that the cytokine levels in serum can be used to predict cancers among subjects age at 80+ y. Our results suggest that latent senescent cancers contribute to age-related chronic inflammation.
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