A5056533507- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Complement system in diseases
- Virology and Viral Diseases
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Mosquito-borne diseases and control
- COVID-19 epidemiological studies
- Chronic Lymphocytic Leukemia Research
- HIV/AIDS Research and Interventions
- COVID-19 Clinical Research Studies
- Viral Infections and Outbreaks Research
- Hepatitis C virus research
- Reproductive System and Pregnancy
- Virus-based gene therapy research
- Viral Infections and Vectors
- CRISPR and Genetic Engineering
- COVID-19 Impact on Reproduction
- Cervical Cancer and HPV Research
- HIV/AIDS drug development and treatment
Ragon Institute of MGH, MIT and Harvard
2015-2023
Beth Israel Deaconess Medical Center
2012-2016
Harvard University
2005-2008
Massachusetts General Hospital
2005-2008
Harvard University Press
2008
Boston University
2005
As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures...
Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded the phase 3 vaccine trials. Data on safety immunogenicity in these populations therefore limited.
Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol boosted AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete 50% vaccinated...
The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions the world where have been deployed. However, wake emergence viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy begun show differences across two approved mRNA platforms, BNT162b2 mRNA-1273; these findings suggest subtle variation immune responses induced by mRNA-1273 may confer differential...
Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in control human immunodeficiency virus (HIV) disease progression exist. We present generated from a Peruvian cohort untreated, clade B-infected subjects, demonstrating that proportion Gag-specific, particular p24-reactive, CTL among virus-specific activity is associated with individuals' CD4 counts viral loads. Analyses second United States confirm these findings point towards dominant...
Abstract Immunodominance is variably used to describe either the most frequently detectable response among tested individuals or strongest within a single individual, yet factors determining inter- intraindividual immunodominance are still poorly understood. More than 90 were against 184 HIV- and 92 EBV-derived, previously defined CTL epitopes. The data show that HLA-B-restricted epitopes significantly more recognized HLA-A- HLA-C-restricted also induced responses of higher magnitude did...
A combination of two Fc antibody features that leverage innate immune function predicts protection from malaria challenge after RTS,S/AS01 vaccination.
An adjuvant composed of saponin and a TLR4 agonist acts by enhancing lymph flow antigen entry into nodes.
Abstract Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples promiscuous I‐restricted exist. To address the extent promiscuity HLA I peptides, responses 242 well‐defined viral were tested in 100 subjects regardless individuals’ type. Surprisingly, half all detected seen absence originally reported restricting allele, and only 3% recognized exclusively presence their original allele. Functional assays confirmed frequent recognition...
Abstract Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions many cases is known rely heavily on the ability interact with a set Ab FcγR expressed innate immune cells. Yet, despite their presumed functional importance, M. mulatta receptors largely uncharacterized, posing fundamental limit ensuring accurate interpretation translation results from this model. In article, we...
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack therapeutics, has paralyzed the globe. Although significant effort been invested in identifying antibodies that block infection, ability to target infected cells through Fc interactions may be vital eliminate virus. To explore role activity SARS-CoV-2 immunity, functional potential cross-SARS-reactive antibody, CR3022, was assessed. CR3022 able broadly drive antibody effector functions,...
ABSTRACT Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, serological marker for closely related HLA-B*1516 and HLA-B*1517 alleles, shares epitope binding motif of HLA-B57 HLA-B58, two that progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses are comparable...
HIV broadly neutralizing antibodies (bnAbs) have been shown to occasionally display unusual virus neutralization profiles with nonsigmoidal slopes and plateaus at <100% against a variety of viruses. The significance incomplete for the ability bnAbs mediate protective effects in vivo, however, is undetermined. In current study, we selected two bnAbs, PGT121 3BNC117, as they incompletely neutralize clade C simian-human immunodeficiency (SHIV) stock (SHIV-327c) 85% 70%, respectively, performed...
Gardasil® (Merck) and Cervarix® (GlaxoSmithKline) both provide protection against infection with Human Papillomavirus 16 (HPV16) 18 (HPV18), that account for around 70% of cervical cancers. Both vaccines have been shown to induce high levels neutralizing antibodies are known protect progression beyond intraepithelial neoplasia grade 2 (CIN2+), although has linked enhanced from progression. However, the transmission-blocking activity HPV, no clear correlate defined may explain persistent...
Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses a superior ability to recognize epitope variants and prevent immune escape. Here, 40 HCV-infected subjects were tested 406 10-mer peptides covering the vast majority of sequence diversity spanning 197-residue region NS3 protein. mounted significantly broader higher functional avidity wider variant...
Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations bulk galactosylation can predict rheumatic flares, act as a sensor for immune activation, gastric cancer relapse, track with biological age, shift vaccination, change HIV reservoir size on therapy, and decrease HCV infections. However, whether changes Fc biology also rebound time remains unclear. The identification of biomarker that could forecast viral significantly accelerate the downselection...
While antiretroviral therapy (ART) has effectively revolutionized HIV care, the virus is never fully eliminated. Instead, immune dysfunction, driven by persistent non-specific activation, ensues and progressively leads to premature immunologic aging. Current biomarkers monitoring changes encompass generic inflammatory biomarkers, that may also change with other infections or disease states, precluding antigen-specific of HIV-infection associated in disease. Given our growing appreciation...
The assessment of cellular anti-viral immunity is often hampered by the limited availability adequate samples, especially when attempting simultaneous, high-resolution determination T cell responses against multiple viral infections. Thus, development assay systems, which optimize usage, while still allowing for detailed breadth and magnitude virus-specific cytotoxic lymphocyte (CTL) responses, urgently needed. This study provides an up-to-date listing currently known, well-defined CTL...