A5007482995- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Immune responses and vaccinations
- CAR-T cell therapy research
- interferon and immune responses
- HIV/AIDS Research and Interventions
- Bioinformatics and Genomic Networks
- Long-Term Effects of COVID-19
- Viral gastroenteritis research and epidemiology
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- Retinal Development and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Advanced Drug Delivery Systems
- Malaria Research and Control
- Immunodeficiency and Autoimmune Disorders
- Complement system in diseases
- SARS-CoV-2 detection and testing
- Reproductive System and Pregnancy
Ragon Institute of MGH, MIT and Harvard
2013-2025
Massachusetts General Hospital
2017-2025
Harvard University
2023-2025
Massachusetts Institute of Technology
2025
MGH Institute of Health Professions
2024
University of Oxford
2008
To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates actions of a large complement interferon effector genes (IEGs) that prevent viral replication. The inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition influenza A virus, dengue West Nile virus replication in vitro. Here we report IFN prevents emergence genomes from endosomal pathway, IFITM3 is both necessary sufficient this function. Notably,...
The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show responses individuals with prior infection, vaccination, both infection boosted vaccination are largely preserved proteins. However, also identify a subset of (∼21%) >50% reduction reactivity spike. Evaluation functional CD4
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort participants with COVID-19. The median times nasal viral RNA culture clearance in immunosuppression due...
Mutationally constrained epitopes of variable pathogens represent promising targets for vaccine design but are not reliably identified by sequence conservation. In this study, we employed structure-based network analysis, which applies theory to HIV protein structure data quantitate the topological importance individual amino acid residues. Mutation residues at important positions disproportionately impaired viral replication and occurred with high frequency in presented protective human...
Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease mortality from coronavirus 2019 (COVID-19), but the immune responses clinical outcomes after acute respiratory syndrome 2 (SARS-CoV-2) infection vaccination yet to be fully defined. Here, we evaluate cellular both SARS-CoV-2 in patients receiving anti-CD20 therapy rituximab (RTX) those low counts due common variable deficiency (CVID) disease. Assessment effector memory CD4 + CD8 T revealed...
The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from infection and vaccine-induced antibody responses, although the extent to which these substitutions in spike non-spike proteins affect T cell recognition is unknown. Here we show responses individuals with prior infection, vaccination, both boosted vaccination are largely preserved proteins. However, also identify a subset of (∼21%) >50% reduction reactivity spike. Evaluation functional CD4 + CD8 memory...
Abstract Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with (88% male) and show that they are composed large clones viral evolution over time those longitudinal samples. We proviruses match RNA ‘producer...
Abstract Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which presenting HLA allele contributes this process unknown. Here we examine CTL response QW9, a epitope presented disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust QW9 persons expressing either allele, T cell receptor (TCR) cross-recognition naturally occurring variant QW9_S3T...
The US National Institute of Allergy and Infectious Diseases (NIAID), part the Health (NIH), convened a virtual workshop on August 8-9th, 2023 to explore potential synergies between HIV vaccine approaches that are designed induce cellular or humoral immune responses. goal this was review data leading candidates discuss best strategies for combining these optimize immunity against HIV. Here, we summarize findings reviewed at knowledge gaps priorities future studies will help accelerate...
Type 1 interferons (IFNs) induce the expression of tripartite interaction motif (TRIM) family E3 ligases, but contribution these antiviral factors to HIV pathogenesis is not completely understood. We hypothesized that increased select type IFN and TRIM isoforms associated with a significantly lower likelihood HIV-1 acquisition viral control during primary infection. measured IFN-α, IFN-β, myxovirus resistance protein A (MxA), human TRIM5α (huTRIM5α), TRIM22 mRNA levels in peripheral blood...
RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and negatives. To ameliorate issues, we combined information from the existing HDF together with new performed multiple orthologous reagents (MORR). In addition being traditionally validated, MORR historical were quantitatively integrated by adaptation an established analysis program, RIGER, for collective interpretation each...
Abstract Background Understanding immunogenicity and effectiveness of SARS-CoV-2 vaccines is critical to guide rational use. Methods We compared the mRNA-1273, BNT-162b2 or Ad26.COV2.S in ambulatory adults Massachusetts, USA. To correlate with three vaccines, we performed an inverse-variance meta-analysis population level from public health reports >40 million individuals. Results A single dose either mRNA vaccine yielded comparable antibody neutralization titers convalescent lower...
Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines viral pathogens. Here, we assess contribution human leukocyte antigen (HLA) class-I-peptide stability 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with processing (TAP)-deficient mono-allelic HLA-expressing lines. We find immunodominant increase surface stabilization class-I molecules in comparison to subdominant epitopes. also strongly correlated overall...
The identification of surfactant protein A (SP-A) as an important innate immune factor the lungs, amniotic fluid, and vaginal tract suggests that it could play role during various stages HIV disease progression transmission. Therefore, we examined whether SP-A bind to also had any effect on viral infectivity. Our data demonstrate binds in a calcium-dependent manner is inhibitable by mannose EDTA. Affinity capture lysate reveals targets envelope glycoprotein (gp120), which was confirmed ELISA...