39 results match your criteria: "Ragon Institute of Massachusetts General Hospital (MGH)[Affiliation]"

scRNA-seq reveals elevated interferon responses and TNF-α signaling via NFkB in monocytes in children with uncomplicated malaria.

Exp Biol Med (Maywood)

January 2025

West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.

Malaria causes significant morbidity and mortality worldwide, disproportionately impacting sub-Saharan Africa. Disease phenotypes associated with infection can vary widely, from asymptomatic to life-threatening. To date, prevention efforts, particularly those related to vaccine development, have been hindered by an incomplete understanding of which factors impact host immune responses resulting in these divergent outcomes.

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Setting the tone: nociceptors as conductors of immune responses.

Trends Immunol

October 2024

Department of Immunology, Harvard Medical School, Boston, MA, USA; The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. Electronic address:

Nociceptors have emerged as master regulators of immune responses in both homeostatic and pathologic settings; however, their seemingly contradictory effects on the functions of different immune cell subsets have been a source of confusion. Nevertheless, work by many groups in recent years has begun to identify patterns of the modalities and consequences of nociceptor-immune system communication. Here, we review recent findings of how nociceptors affect immunity and propose an integrated concept whereby nociceptors are neither inherently pro- nor anti-inflammatory.

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Background: Households are a major setting for SARS-CoV-2 infections, but there remains a lack of knowledge regarding the dynamics of viral transmission, particularly in the setting of widespread pre-existing SARS-CoV-2 immunity and evolving variants.

Methods: We conducted a prospective, case-ascertained household transmission study in the greater Boston area in March-July 2022. Anterior nasal swabs, along with clinical and demographic data, were collected for 14 days.

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Background: Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.

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Background: Developing a cure for HIV remains a global scientific priority. In 2022, the Females Rising through Education, Support and Health (FRESH) cohort launched an HIV cure-related trial involving an analytical treatment interruption (ATI) in Durban, South Africa.

Objectives: To explore community perspectives about HIV cure-related research.

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Natural killer (NK) cells play an important role in immune rejection in solid organ transplantation. To mitigate human NK cell activation in xenotransplantation, introducing inhibitory ligands on xenografts genetic engineering of pigs may protect the graft from human NK cell-mediated cytotoxicity and ultimately improve xenograft survival. In this study, non-classical HLA class I molecules HLA-E and HLA-G were introduced in an immortalized porcine liver endothelial cell line with disruption of five genes (, , , , and ) encoding three major carbohydrate xenoantigens (αGal, Neu5Gc, and Sda) and swine leukocyte antigen class I (SLA-I) molecules.

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Article Synopsis
  • The study focuses on how antibodies are characterized using B cells and highlights the challenges with analyzing plasma cells due to their lack of surface B cell receptors (BCRs).
  • Researchers explored the antibody repertoires from bone marrow and spleen in a mouse model, overcoming technical limitations to include plasma cells in their analysis.
  • Results showed that spleen B cells produced higher affinity antibodies than bone marrow plasma cells, with evidence of shared origins for some antibody clones between the two lymphoid tissues.
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Knowledge of aging biology needs to be expanded due to the continuously growing number of elderly people worldwide. Aging induces changes that affect all systems of the body. The risk of cardiovascular disease and cancer increases with age.

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Introduction: Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown.

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Background: Pediatric patients with cancer infected with COVID-19 may be at higher risk of severe disease and may be unable to mount an adequate response to the virus due to compromised immunity secondary to their cancer therapy.

Procedure: This study presents immunologic analyses of 20 pediatric patients with cancer, on active chemotherapy or having previously received chemotherapy, and measures their immunoglobulin titers and activation of cellular immunity response to acute SARS-CoV-2 infection and COVID-19 vaccination compared with healthy pediatric controls.

Results: Forty-three patients were enrolled, of which 10 were actively receiving chemotherapy, 10 had previously received chemotherapy, and 23 were healthy controls.

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Article Synopsis
  • The immune system protects the body from infections and tumors while maintaining balance, while the somatosensory nervous system gathers sensory info to help react to harmful situations.
  • These two systems can work together as an "integrated defense system," with nociceptors detecting harmful stimuli and influencing immune responses positively or negatively.
  • The review discusses the current knowledge of how nociceptors interact with myeloid cells of the innate immune system, especially in barrier tissues, and highlights ongoing questions in the rapidly evolving field of peripheral neuroimmunology.
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Efficient isolation of rare B cells using next-generation antigen barcoding.

Front Cell Infect Microbiol

March 2023

Department of Immunology and Microbiology, Scripps Research, La Jolla, CA, United States.

Article Synopsis
  • Efficiently isolating antigen-specific B cells can speed up the discovery of therapeutic monoclonal antibodies (mAbs) and improve vaccine development.
  • Traditional methods for mAb discovery are time-consuming and expensive, but new techniques in single-cell genomics enable the processing of thousands of cells at once.
  • The introduced method combines antigen barcoding and computational tools to analyze large numbers of B cells, successfully recovering thousands of mAbs, including rare precursors for key HIV-neutralizing antibodies.
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Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145).

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Introduction: Spontaneous control of HIV-1 replication in the absence of anti-retroviral therapy (ART) naturally occurs in a small proportion of HIV-1-infected individuals known as elite controllers (EC), likely as a result of improved innate and adaptive immune mechanisms. Previous studies suggest that enhanced cytosolic immune recognition of HIV-1 reverse transcripts in conventional dendritic cells (mDC) from EC enables effective induction of antiviral effector T cell responses. However, the specific molecular circuits responsible for such improved innate recognition of HIV-1 in mDC from these individuals remain unknown.

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Article Synopsis
  • Continuous emergence of SARS-CoV-2 variants poses challenges for vaccine effectiveness, diagnostics, and treatments, raising concerns about a potential new highly transmissible and fatal betacoronavirus.
  • The study utilized yeast display technology and next-generation sequencing to analyze the specificity of antibodies from two convalescent donors, focusing on their responses to SARS-CoV-2 variants and other betacoronaviruses.
  • Most antibodies from the patients were found to be non-neutralizing, and the degree of somatic hypermutation varied significantly between the individuals, providing insights that could inform strategies against emerging coronavirus threats.
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Since the emergence of SARS-CoV-2 (SARS-2), multiple vaccine candidates were developed and studied both preclinically and clinically. Nearly all are based on the SARS-2 spike glycoprotein or its receptor binding domain (RBD). Studies of these vaccine candidates have largely been in a SARS-2 naïve context.

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We measured viral kinetics of SARS-CoV-2 Omicron infection in 36 mRNA-vaccinated individuals, 11 of whom were treated with nirmatrelvir-ritonavir (NMV-r). We found that NMV-r was associated with greater incidence of viral rebound compared to no treatment. For those that did not rebound, NMV-r significantly reduced time to PCR conversion.

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We enrolled 7 individuals with recurrent symptoms or antigen test conversion following nirmatrelvir-ritonavir treatment. High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis.

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Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with (Mtb), that results either in a latent or active form of disease, the latter associated with Mtb spread. In the absence of an effective vaccine, epidemiologic modeling suggests that aggressive treatment of individuals with active TB (ATB) may curb spread.

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Comprehensive Oncogenic Features of Coronavirus Receptors in Glioblastoma Multiforme.

Front Immunol

April 2022

Department of Diagnostics, Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China.

The COVID-19 pandemic caused by SARS-CoV-2 infection has placed health systems under excessive pressure and especially elderly people with cancer. Glioblastoma multiforme (GBM) is a malignant brain tumor with an increasing incidence in elderly individuals, and thereby GBM patients are a vulnerable population during the COVID-19 outbreak. Accumulating studies have implied that SARS-CoV-2 might invade the brain directly coronavirus receptors.

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A virosomal vaccine inducing systemic/mucosal anti-HIV-1 gp41 IgG/IgA had previously protected Chinese-origin rhesus macaques (RMs) against vaginal SHIV challenges. Here, we assessed its efficacy in Indian-origin RMs by intramuscular priming/intranasal boosting (n=12/group). Group K received virosome-P1-peptide alone (harboring the Membrane Proximal External Region), Group L combined virosome-rgp41 plus virosome-P1, and Group M placebo virosomes.

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Article Synopsis
  • * This study explored the role of Natural Killer (NK) cells in HIV-1 persistence during long-term ART, using advanced techniques like twin mass cytometry to analyze their receptor-ligand interactions in individuals already on ART.
  • * Findings revealed that specific NK cell receptors and ligands, such as CD58 and certain killer cell immunoglobulin-like receptors (KIRs), were predictive of HIV-1 persistence, while a less mature NK cell phenotype was linked to lower levels of HIV-1 DNA in patients.
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Identification and Tracking of Alloreactive T Cell Clones in Rhesus Macaques Through the RM-scTCR-Seq Platform.

Front Immunol

February 2022

Division of Pediatric Hematology/Oncology, Boston Children's Hospital; Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.

T cell receptor (TCR) clonotype tracking is a powerful tool for interrogating T cell mediated immune processes. New methods to pair a single cell's transcriptional program with its TCR identity allow monitoring of T cell clonotype-specific transcriptional dynamics. While these technologies have been available for human and mouse T cells studies, they have not been developed for Rhesus Macaques (RM), a critical translational organism for autoimmune diseases, vaccine development and transplantation.

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SARS-CoV-2 entry into host cells is a crucial step for virus tropism, transmission, and pathogenesis. Angiotensin-converting enzyme 2 (ACE2) has been identified as the primary entry receptor for SARS-CoV-2; however, the possible involvement of other cellular components in the viral entry has not yet been fully elucidated. Here we describe the identification of vimentin (VIM), an intermediate filament protein widely expressed in cells of mesenchymal origin, as an important attachment factor for SARS-CoV-2 on human endothelial cells.

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