A5076243921- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Hepatitis C virus research
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Hepatitis B Virus Studies
- T-cell and B-cell Immunology
- Malaria Research and Control
- Mosquito-borne diseases and control
- Influenza Virus Research Studies
- HIV-related health complications and treatments
- HIV, Drug Use, Sexual Risk
- RNA Interference and Gene Delivery
- Herpesvirus Infections and Treatments
- Pharmacogenetics and Drug Metabolism
- CAR-T cell therapy research
- Virology and Viral Diseases
- Respiratory viral infections research
- Antibiotics Pharmacokinetics and Efficacy
- Monoclonal and Polyclonal Antibodies Research
Moderna Therapeutics (United States)
2022-2025
GlaxoSmithKline (United States)
2018-2024
University of Maryland, Baltimore
2023
Universities at Shady Grove
2021
Armed Forces Research Institute of Medical Science
2006-2019
Walter Reed Army Institute of Research
2001-2018
National Institutes of Health
2014-2017
The University of Sydney
1956-2015
Ospedale Sacro Cuore Don Calabria
2015
Salford Royal NHS Foundation Trust
2015
The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control.In community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections recombinant canarypox vector (ALVAC-HIV [vCP1521]) plus two booster glycoprotein 120 subunit (AIDSVAX B/E). placebo were administered 16,402 healthy men women between ages 18 30 years in Rayong Chon Buri provinces Thailand....
In the RV144 trial, estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed case–control analysis to identify antibody and cellular immune correlates infection risk.
ABSTRACT The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers diverse epidemiological regions were screened using pseudovirus panels composed clades A, B, C, D circulating recombinant forms (CRFs)....
Background Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic virologic following infection investigates usage of a novel strategy. Methods Findings We prospectively screened 24,430 subjects in Bangkok identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 II, 15 III, 2 IV) whom completed 24 weeks megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc)....
Background. Three full doses of RTS,S/AS01 malaria vaccine provides partial protection against controlled human parasite infection (CHMI) and natural exposure. Immunization regimens, including a delayed fractional third dose, were assessed for potential increased immunologic responses. Methods. In phase 2a, controlled, open-label, study healthy malaria-naive adults, 16 subjects vaccinated with 0-, 1-, 2-month full-dose regimen (012M) 30 who received 7-month regimen, dose (Fx017M), underwent...
Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of safety, reactogenicity, humoral immunogenicity quadrivalent messenger RNA (mRNA) against seasonal influenza, mRNA-1010, from first 2 parts 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In placebo-controlled Part 1, single dose mRNA-1010 (50 µg, 100 or 200 µg) elicited...
The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against gp120 envelope (Env). Peptide microarray analysis six subtypes group M consensus that vaccination induced to the second variable (V2) loop of multiple subtypes. We further evaluated V2 by ELISA surface plasmon resonance...
The interaction between follicular T helper cells (TFH) and B in the lymph nodes spleen has a major impact on development of antigen-specific cell responses during infection or vaccination. Recent studies described functional equivalent these among circulating CD4 cells, referred to as peripheral TFH cells. Here, we characterize phenotype vitro activity populations, well effect HIV populations. In co-culture experiments confirmed CXCR5+ from HIV-uninfected donors provide help more...
LN inflammation in chronic HIV is associated with accumulation of follicular CD8 T cells that could be redirected to kill infected cells.
The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX B/E was, to our knowledge, the first demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies IFN-γ ELISPOT was performed on PBMCs from HIV-1-uninfected (n = 61) placebo 10) recipients HIV-1 Env peptides. Positive measured in 25 (41%) vaccinees predominantly CD4(+) cell-mediated. Responses targeted within region, with 15 of...
Abstract Background Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)–based quadrivalent seasonal vaccine, mRNA-1010, was investigated in first-in-human, phase 1/2 clinical trial conducted 3 parts. Methods In parts 1 to of this stratified observer-blind study, adults aged ≥18 years were randomly assigned receive single dose (6.25–200 µg) mRNA-1010 or placebo (part 1) an active comparator (Afluria; 2 and 3). Primary study objectives assessment safety,...
Blood samples were taken from 20 horses competing in a 100 km endurance ride and plasma concentrations of sodium, potassium, chloride, bicarbonate protein measured. Measurements performed on before the (pre-ride), at mid point end after 30 min recovery period (post-ride). Sweat collected 6 14 3-day event competition sweat potassium chloride There substantial decreases electrolyte concentrations, which greater than previously reported. Decreases pre to post 5 mmol/1 1.2 16 found. These losses...
Primaquine (PQ) metabolism by the cytochrome P450 (CYP) 2D family of enzymes is required for antimalarial activity in both humans (2D6) and mice (2D). Human CYP 2D6 highly polymorphic, decreased enzyme has been linked to PQ activity. Despite importance efficacy, exact role that these play pharmacokinetics not extensively studied vivo. In this study, a series pharmacokinetic experiments were conducted with differential characteristics, including wild-type (WT), knockout (KO), humanized...
Abstract The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies exceptional breadth. MPER usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some polyreactive, such 4E10. Here we describe an broadly antibody major IgG1 PGZL1, which shares V/D-region genes with 4E10, has a shorter CDRH3, is less polyreactive. A recombinant sublineage variant...
The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses these vaccines and development new variant-derived ones
The development of an effective HIV-1 vaccine is critical to control the pandemic. A prime-boost trial assessing safety and immunogenicity was conducted in Thailand as part evaluation candidate regimens for a phase 3 efficacy trial.ALVAC-HIV (vCP1521), expressing circulating recombinant form 01_AE (CRF01_AE) gp120/subtype B LAI subtype Gag/Protease boosted with envelope oligomeric CRF01_AE gp160 (ogp160) or bivalent CRF01_AE/subtype gp120 CM235/SF2, evaluated 1/II 130 HIV-negative Thai...
Background We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, candidate HIV-1 vaccine based on recombinant modified vaccinia Ankara viral vector expressing genes env/gag/pol. The HIV sequences were derived from circulating form CRF01_AE, which predominates in Thailand. objective was to evaluate safety and immunogenicity MVA-CMDR human volunteers the US Methodology/Principal Findings or placebo administered intra-muscularly (IM; 107 108 pfu) intradermally...
Background. The Thai Phase III Trial of ALVAC-HIV and AIDSVAX B/E showed an estimated vaccine efficacy (VE) 31% to prevent acquisition human immunodeficiency virus (HIV). Here we evaluated the effect vaccination on disease progression after infection. Methods. CD4+ T-cell counts HIV viral load (VL) were measured serially. primary analysis (VEP) as percent reduction (vaccine vs placebo) in cumulative probability a composite endpoint clinical count components at prespecified time points...
Background A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks gp120 AIDSVAX B/E 12 demonstrated modest efficacy of 31.2% for prevention HIV acquisition in HIV-uninfected adults participating a community-based trial Thailand. Methodology/Principal Findings Reactogenicity was recorded 3 days following vaccination. Adverse events were monitored every 6 months 3.5 years, during which pregnancy outcomes recorded. Of the 16,402...
ABSTRACT Cytochrome P450 (CYP) 2D metabolism is required for the liver-stage antimalarial efficacy of 8-aminoquinoline molecule tafenoquine in mice. This could be problematic Plasmodium vivax radical cure, as human CYP ortholog (2D6) highly polymorphic. Diminished 2D6 enzyme activity, poor-metabolizer phenotype, compromise curative humans. Despite importance efficacy, exact role that plays and pharmacokinetics other molecules has not been extensively studied. In this study, a series...