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Columbia University (46)
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Immport Dataset Available (118)
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Wimmers F, Burrell AR, Feng Y, Zheng H, Arunachalam PS, Hu M, Spranger S, Nyhoff LE, Joshi D, Trisal M, Awasthi M, Bellusci L, Ashraf U, Kowli S, Konvinse KC, Yang E, Blanco M, Pellegrini K, Tharp G, Hagan T, Chinthrajah RS, Nguyen TT, Grifoni A, Sette A, Nadeau KC, ...
Cell
2023-10-12
PMID: 37776858
Adult
Child
Child, Preschool
COVID-19
Cytokines
HIPC 3 (2022)
Humans
Immunity, Mucosal
Infant
Interferon-alpha
Multiomics
SARS-CoV-2
Stanford
Abstract:
The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell multi-omics. Together, these data provide a snapshot of immunity to infection during the initial weeks and months of life.
Yates JL, Hunt DT, Kulas KE, Chave KJ, Styer L, Chakravarthi ST, Cai GY, Bermúdez-González MC, Kleiner G, Altman D, Srivastava K, Simon V, Feihel D, McGowan J, Hogrefe W, Noone P, Egan C, Slifka MK, Lee WT
Journal of medical virology
2023-10-01
PMID: 37805977
Asymptomatic Infections
Biological Assay
Cross Reactions
HIPC 3 (2022)
Humans
Icahn School of Medicine at Mount Sinai
Monkeypox
Orthopoxvirus
Retrospective Studies
Abstract:
In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 104 nonendemic locations worldwide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.
Ockene MW, Russo SC, Lee H, Monthé-Drèze C, Stanley TL, Ma IL, Toribio M, Shook LL, Grinspoon SK, Edlow AG, Fourman LT
The Journal of clinical endocrinology and metabolism
2023-09-18
PMID: 36988326
Birth Weight
Body Mass Index
Cardiovascular Diseases
Child
COVID-19
Female
HIPC 3 (2022)
Humans
Infant
Infant, Newborn
Longitudinal Studies
Massachusetts Institute of technology
Pregnancy
Weight Gain
Abstract:
[{'@Label': 'CONTEXT', '#text': 'Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown.'}, {'@Label': 'OBJECTIVE', '#text': 'To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.'}, {'@Label': 'METHODS', '#text': 'We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding.'}, {'@Label': 'RESULTS', '#text': 'Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: -0.35, 95% CI -0.66 to -0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02).'}, {'@Label': 'CONCLUSION', '#text': 'Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.'}]
Gervais A, Rovida F, Avanzini MA, Croce S, Marchal A, Lin SC, Ferrari A, Thorball CW, Constant O, Le Voyer T, Philippot Q, Rosain J, Angelini M, Pérez Lorenzo M, Bizien L, Achille C, Trespidi F, Burdino E, Cassaniti I, Lilleri D, Fornara C, Sammartino JC, Cereda D, Marrocu C, Piralla A, ...
The Journal of experimental medicine
2023-09-04
PMID: 37347462
Animals
Antibodies, Viral
Autoantibodies
Chlorocebus aethiops
HIPC 3 (2022)
Humans
Interferon-alpha
Interferon Type I
Vero Cells
West Nile Fever
West Nile virus
Yale University
Abstract:
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre NC, Lutz R, Cruz I, Raddassi K, Ruff WE, Racke MK, Wilson JE, Givens TS, Grifoni A, Weiskopf D, Sette A, Kleinstein SH, Montgomery RR, Shaw AC, Li F, Fan R, Hafler DA, Tomayko MM, Longbrake EE
JCI insight
2023-08-22
PMID: 37606046
Aged
Antibodies, Monoclonal
Antibody Formation
Antilymphocyte Serum
BNT162 Vaccine
COVID-19
HIPC 3 (2022)
Humans
RNA, Messenger
SARS-CoV-2
Vaccination
Yale University
Abstract:
BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTSIn contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell-depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell-depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSIONThese results demonstrate that serial vaccination strategies can be effective for a subset of B cell-depleted patients.FUNDINGThe NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).
Mayer-Blackwell K, Ryu H, Codd AS, Parks KR, MacMillan HR, Cohen KW, Stewart TL, Seese A, Lemos MP, De Rosa SC, Czartoski JL, Moodie Z, Nguyen LT, McGuire DJ, Ahmed R, Fiore-Gartland A, McElrath MJ, Newell EW
Cell reports. Medicine
2023-08-15
PMID: 37552991
CD8-Positive T-Lymphocytes
COVID-19
Epitopes
HIPC 3 (2022)
Humans
Leukocyte Common Antigens
Memory T Cells
SARS-CoV-2
Seattle Children's Research Institute
Vaccination
Abstract:
SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8+ T cell vaccine-response magnitudes. Comparing baseline with post-vaccination TCRβ repertoires, we observed large clonotypic expansions correlated with the frequency of spike-specific T cells. Epitope mapping the largest CD8+ T cell responses confirms that an HLA-A∗03:01 epitope was highly immunodominant. Peptide-MHC tetramer staining together with mass cytometry and single-cell sequencing permit detailed phenotyping and clonotypic tracking of these S-specific CD8+ T cells. Our results demonstrate that infection-induced S-specific CD8+ T cell memory plays a significant role in shaping the magnitude and clonal composition of the circulating T cell repertoire after vaccination, with mRNA vaccination promoting CD8+ memory T cells to a TEMRA-like phenotype.
Connors TJ, Matsumoto R, Verma S, Szabo PA, Guyer R, Gray J, Wang Z, Thapa P, Dogra P, Poon MML, Rybkina K, Bradley MC, Idzikowski E, McNichols J, Kubota M, Pethe K, Shen Y, Atkinson MA, Brusko M, Brusko TM, Yates AJ, Sims PA, Farber DL
Immunity
2023-08-08
PMID: 37421943
CD8-Positive T-Lymphocytes
Child
Child, Preschool
Columbia University
HIPC 3 (2022)
Humans
Immunologic Memory
Infant
Infant, Newborn
Lymphoid Tissue
Memory T Cells
Mucous Membrane
Receptors, Antigen, T-Cell
Abstract:
Infancy and childhood are critical life stages for generating immune memory to protect against pathogens; however, the timing, location, and pathways for memory development in humans remain elusive. Here, we investigated T cells in mucosal sites, lymphoid tissues, and blood from 96 pediatric donors aged 0-10 years using phenotypic, functional, and transcriptomic profiling. Our results revealed that memory T cells preferentially localized in the intestines and lungs during infancy and accumulated more rapidly in mucosal sites compared with blood and lymphoid organs, consistent with site-specific antigen exposure. Early life mucosal memory T cells exhibit distinct functional capacities and stem-like transcriptional profiles. In later childhood, they progressively adopt proinflammatory functions and tissue-resident signatures, coincident with increased T cell receptor (TCR) clonal expansion in mucosal and lymphoid sites. Together, our findings identify staged development of memory T cells targeted to tissues during the formative years, informing how we might promote and monitor immunity in children.
Rybkina K, Bell JN, Bradley MC, Wohlbold T, Scafuro M, Meng W, Korenberg RC, Davis-Porada J, Anderson BR, Weller RJ, Milner JD, Moscona A, Porotto M, Luning Prak ET, Pethe K, Connors TJ, Farber DL
The Journal of experimental medicine
2023-08-07
PMID: 37133746
Child
Columbia University
COVID-19
HIPC 3 (2022)
Humans
Inflammation
SARS-CoV-2
Severity of Illness Index
Abstract:
SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.
Matsumoto R, Gray J, Rybkina K, Oppenheimer H, Levy L, Friedman LM, Khamaisi M, Meng W, Rosenfeld AM, Guyer RS, Bradley MC, Chen D, Atkinson MA, Brusko TM, Brusko M, Connors TJ, Luning Prak ET, Hershberg U, Sims PA, Hertz T, Farber DL
Nature immunology
2023-08-01
PMID: 37460638
Adult
B-Lymphocytes
Bronchi
Child
Child, Preschool
Columbia University
COVID-19
HIPC 3 (2022)
Humans
Infant
Lymph Nodes
Lymphoid Tissue
Abstract:
Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0-13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4+ T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and immunoglobulin class switching and exhibit a more activated profile than lymph node B cells. Moreover, B cells in the lung and lung-associated lymph nodes generate biased antibody responses to multiple respiratory pathogens compared to circulating antibodies, which are mostly specific for vaccine antigens in the early years of life. Together, our findings provide evidence for BALT as an early life adaptation for mobilizing localized immune protection to the diverse respiratory challenges during this formative life stage.
Sulczewski FB, Maqueda-Alfaro RA, Alcántara-Hernández M, Perez OA, Saravanan S, Yun TJ, Seong D, Arroyo Hornero R, Raquer-McKay HM, Esteva E, Lanzar ZR, Leylek RA, Adams NM, Das A, Rahman AH, Gottfried-Blackmore A, Reizis B, Idoyaga J
Nature immunology
2023-08-01
PMID: 37414907
Animals
Antiviral Agents
Bone Marrow
Cell Differentiation
Columbia University
Dendritic Cells
HIPC 3 (2022)
Mice
Abstract:
High-dimensional approaches have revealed heterogeneity amongst dendritic cells (DCs), including a population of transitional DCs (tDCs) in mice and humans. However, the origin and relationship of tDCs to other DC subsets has been unclear. Here we show that tDCs are distinct from other well-characterized DCs and conventional DC precursors (pre-cDCs). We demonstrate that tDCs originate from bone marrow progenitors shared with plasmacytoid DCs (pDCs). In the periphery, tDCs contribute to the pool of ESAM+ type 2 DCs (DC2s), and these DC2s have pDC-related developmental features. Different from pre-cDCs, tDCs have less turnover, capture antigen, respond to stimuli and activate antigen-specific naïve T cells, all characteristics of differentiated DCs. Different from pDCs, viral sensing by tDCs results in IL-1β secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDCs are a distinct pDC-related subset with a DC2 differentiation potential and unique proinflammatory function during viral infections.
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