A5077517503- HIV Research and Treatment
- Virology and Viral Diseases
- Down syndrome and intellectual disability research
- Fermentation and Sensory Analysis
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Microbial Metabolic Engineering and Bioproduction
- Wine Industry and Tourism
- Fungal and yeast genetics research
- Horticultural and Viticultural Research
- HIV/AIDS drug development and treatment
- Virus-based gene therapy research
- RNA Research and Splicing
- Medical Coding and Health Information
- Viral Infections and Outbreaks Research
- Chronic Disease Management Strategies
- Hepatitis B Virus Studies
- Disability Education and Employment
- Monoclonal and Polyclonal Antibodies Research
- Metalloenzymes and iron-sulfur proteins
- Immunodeficiency and Autoimmune Disorders
- Biofuel production and bioconversion
- T-cell and B-cell Immunology
- Fatty Acid Research and Health
- Vibrio bacteria research studies
International AIDS Vaccine Initiative
2010-2024
Boston Children's Hospital
2015-2024
Desmond Tutu HIV Foundation
2016
Aurum Institute
2016
Beth Israel Deaconess Medical Center
2016
University of Cape Town
2016
Kenya AIDS Vaccine Initiative
2016
Perinatal HIV Research Unit
2016
National Institute of Allergy and Infectious Diseases
2016
New York Proton Center
2011
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01
Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele usage and...
The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need be matured, through additional heterologous immunizations, into are able produce broadly neutralizing antibodies. CD4 T cell help will critical for the development of such high-affinity antibody responses. Thus, we assessed induction and epitope specificities vaccine-specific from IAVI G001 phase 1 clinical trial tested immunization...
Background: A prophylactic HIV-1 vaccine is a global health priority. Objective: To assess novel platform as regimen. Design: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149) Setting: United States, East Africa, South Africa. Patients: Healthy adults without HIV infection. Intervention: 2 vaccines (adenovirus serotype 26 with an envelope insert [Ad26.EnvA] adenovirus 35...
We describe the cloning and characterization of complete gene for iron-sulfur protein subunit succinate dehydrogenase (EC 1.3.99.1) from Saccharomyces cerevisiae. The promoter coding sequence have been cloned into an Escherichia coli-yeast shuttle vector. complements defect in a dehydrogenase-deficient yeast mutant isolated by us, expression is fully responsive to induction glucose deprivation, indicating that intact.
A recombinant modified vaccinia Ankara virus vaccine candidate (TBC-M4) expressing HIV-1 subtype C env, gag, tat-rev, and nef-RT genes was tested in a randomized, double-blind, dose escalation Phase I trial 32 HIV-uninfected healthy volunteers who received three intramuscular injections of TBC-M4 at 0, 1, 6 months 5 × 107 plaque-forming units (pfu) (low dosage, LD) (n = 12) or 2.5 108 pfu (high HD) placebo 8). Local systemic reactogenicity experienced by approximately 67% 83% recipients,...
Objectives: Children with Down syndrome (DS) have increased difficulty initiating and maintaining sleep (DIMS), excessive daytime sleepiness (EDS), obstructive apnea (OSA). As part of a quality improvement initiative, parents children enrolled in the Children’s Hospital Boston Syndrome Program were surveyed about their child’s breathing patterns while asleep. Methods: An anonymous Internet-based questionnaire was used study. Results: The completion rate 46.5% (255/548). DIMS EDS...
Background We conducted a Phase I dose-escalation trial of ADMVA, Clade-B'/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in modified vaccinia Ankara viral vector. Sequences were derived from prevalent circulating recombinant form Yunnan, China, an area high HIV incidence. The objective was to evaluate the safety immunogenicity ADMVA human volunteers. Methodology/Principal Findings or placebo administered intramuscularly at months 0, 1 6 50 healthy adult volunteers...
We have examined the expression of gene encoding iron-protein subunit (Ip) succinate dehydrogenase in Saccharomyces cerevisiae. The had been cloned by us and shown to be subject glucose regulation (A. Lombardo, K. Carine, I. E. Scheffler, J. Biol. Chem. 265:10419-10423, 1990). discovered that a significant part Ip mRNA levels involves turnover rate this mRNA. In presence glucose, half-life appears less than 5 min, while glycerol medium, is greater 60 min. also regulated transcriptionally...
Background We conducted a Phase I dose escalation trial of ADVAX, DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from prevalent circulating recombinant form in Yunnan, China, an area high incidence. The objective was to evaluate the safety immunogenicity ADVAX human volunteers. Methodology/Principal Findings or placebo administered intramuscularly at months 0, 1 3 45 healthy volunteers not risk for HIV-1. Three dosage levels...
The goals of this undertaking were to assess the outcomes thyroid screening tests and adherence guidelines across five Down syndrome (DS) specialty clinics in various states. Data related collected for 663 individuals specializing comprehensive care with DS a period 1 year. Of participants, 47.7% participants had TSH free T4 ordered at their clinic visit. Approximately 19.0% (60/316) new disorder diagnosis made. We conclude that sizable proportion patients are not up‐to‐date on current when...
We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency type 1 (HIV-1) vaccine. Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, United Kingdom were assigned to receive 4 prime-boost regimens (administered at 0 months, respectively; ratio vaccine placebo recipients, 12:4): priming with lower-dose SeV-Gag given intranasally, followed by boosting an adenovirus...
Background Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against in humans. We recently developed a replication-competent, highly Ad26 vector expresses mosaic Env (rcAd26.MOS1.HIV-Env, "rcAd26"). Here we present the results of first-in-human, placebo-controlled clinical trial test safety, immunogenicity and mucosal shedding rcAd26 given orally. Methods Healthy adults were randomly assigned receive...
A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01 , induced precursors of VRC01-class at high frequency majority recipients. These precursors, that target CD4 receptor binding site, had undergone...
Background Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing A Gag, Int and Nef (Ad35-GRIN) may lead to unique immune profile, inducing both strong T-cell antibody responses. Methods In phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized one four regimens: heterologous with two doses F4/AS01E F4/AS01B followed...
We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1 vaccine candidate germline targeting priming immunogen. Production was carried out via transient expression in human embryonic kidney 293 (HEK293) cell line followed by combination purification techniques. A large-scale cGMP (200 L) run yielded 354 mg purified 60mer drug product material, which formulated at 1 mg/mL 10%...
ABSTRACT A randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses DNA vaccine (Advax) plus 1 dose recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or TBC-M4 alone (groups B, respectively). Both regimens were found be safe well tolerated. Gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay responses detected 1/10 (10%) individuals group after three Advax...
Abstract Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele...
AbstractA Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV not known to cause disease in humans. Because it genetically and antigenically related human parainfluenza type 1 (hPIV-1), important determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a vector-based vaccine. To quantify neutralizing (NAb) serum, sensitive neutralization assay was using encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects...
The Down Syndrome Study Group (DSSG) was founded in 2012 as a voluntary, collaborative effort with the goal of supporting evidenced-based health care guidelines for individuals syndrome (DS). Since then, 5 DS specialty clinics have collected prospective, longitudinal data on medical conditions that co-occur DS. Data were entered by clinical staff or trained designees into National Patient Database, which we created using REDCap software. In our pilot year, enrolled 663 participants across...
The main purposes of this undertaking were to determine how often patients with Down syndrome (DS) are screened for celiac disease (CD) across five DS specialty clinics, which symptoms CD most reported providers at these and, many individuals diagnosed by clinics. This was accomplished following 663 1 year, clinics in different states specializing the comprehensive care people DS. Of participants, 114 their visit a clinic. Protracted constipation (43.2%) and refractory behavioral problems...
Abstract Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study their occurrence impact on outcomes. We describe the prevalence relationships medical, (ND), mental health (MH) conditions in children DS. created prospective clinical database individuals DS, integrated into workflow specialty Syndrome Program at pediatric referral hospital. Conditions were collected through caregiver‐ clinician report visits ( N =...
Abstract A partial cDNA clone corresponding to the iron-sulfur protein of succinate dehydrogenase (EC 1.3.99.1) has been isolated by an application polymerase chain reaction (Gould, S. J., Subramani, S., and Scheffler, I. E. (1989) Proc. Natl. Acad. Sci. U. A. 86, 1934-1938). We used this for targeted gene disruption isolate clones Saccharomyces cerevisiae which were totally defective in enzyme. The was verified Southern analysis. Northern analysis revealed existence a new transcript...
Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into specialty Syndrome Program, the goals of better understanding incidence, course, impact co-occurring neurodevelopmental, mental health conditions in DS. We describe process developing database, including systematic approach to data collection infrastructure, report on feasibility, challenges, solutions initial...