A5016914691- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Vitamin C and Antioxidants Research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hepatitis C virus research
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- Immune Response and Inflammation
- Sphingolipid Metabolism and Signaling
- HIV/AIDS Research and Interventions
- Cutaneous lymphoproliferative disorders research
- Viral Infections and Immunology Research
- Retinoids in leukemia and cellular processes
- CAR-T cell therapy research
- Animal Virus Infections Studies
- Lipid Membrane Structure and Behavior
- Blood groups and transfusion
- Antimicrobial Peptides and Activities
- SARS-CoV-2 and COVID-19 Research
- T-cell and Retrovirus Studies
- Herpesvirus Infections and Treatments
Walter Reed Army Institute of Research
2006-2023
Armed Forces Research Institute of Medical Science
2012-2023
Henry M. Jackson Foundation
2021
United States Army
2012-2015
United States Department of the Army
2012
Memorial Sloan Kettering Cancer Center
1993-2008
Queens College, CUNY
1996-1999
The Graduate Center, CUNY
1996-1999
City University of New York
1996
The University of Texas MD Anderson Cancer Center
1995
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 Dengue is a major health threat and the number of symptomatic infections caused by four dengue serotypes estimated to be 96 million 1 with annually around 10,000 deaths 2 . However, no antiviral drugs are available for treatment or prophylaxis dengue. We recently described interaction between non-structural proteins NS3 NS4B as promising target development pan-serotype virus (DENV) inhibitors 3 Here we present JNJ-1802—a highly potent DENV inhibitor that blocks NS3–NS4B within viral...
Abstract Vitamin C is an antioxidant vitamin that has been hypothesized to antagonize the effects of reactive oxygen species–generating antineoplastic drugs. The therapeutic efficacy widely used drugs doxorubicin, cisplatin, vincristine, methotrexate, and imatinib were compared in leukemia (K562) lymphoma (RL) cell lines with without pretreatment dehydroascorbic acid, commonly transported form C. effect on viability, clonogenicity, apoptosis, P-glycoprotein, species (ROS), mitochondrial...
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 RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B E) was previously shown to have 31.2% efficacy rate. Plasma specimens from vaccine placebo recipients were used in an extensive set assays identify correlates HIV-1 infection risk. Of six primary variables that studied, only one displayed significant inverse correlation with risk infection: the antibody (Ab) response fusion protein containing V1 V2 regions...
Emergence of novel variants the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores need for next-generation vaccines able to elicit broad and durable immunity. Here we report evaluation a ferritin nanoparticle vaccine displaying receptor-binding domain SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination macaques using two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses reciprocal peak mean...
Human interferon-inducible protein 10 (IP-10), a member of the family small secreted proteins called intercrine cytokines or chemokines, is by interferon gamma-stimulated T cells, monocytes, endothelial and keratinocytes. We have begun to explore biological properties IP-10 cloning overexpression in baculovirus bacterial expression systems. A 9.9-kD was infected insect which on sodium dodecyl sulfate-polyacrilamide gel electrophoresis comigrated with keratinocyte f(22-98), recombinant...
The RV144 ALVAC-HIV prime, AIDSVAX B/E boost afforded 60% efficacy against human immunodeficiency virus (HIV) acquisition at 1 year, waning to 31.2% after 3.5 years. We hypothesized that additional vaccinations might augment immune correlates of protection.In a randomized placebo-controlled double-blind study 162 HIV-negative vaccine recipients, we evaluated 2 boosts, given 6-8 years since vaccination, for safety and immunogenicity, weeks 0 24. Study groups 1-3 received ALVAC-HIV+AIDSVAX...
To evaluate the role of V3-specific IgG antibodies (Abs) in RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic peptides (cV3s) from diverse virus subtypes. Sieve analysis CRF01_AE breakthrough viruses 43 vaccine- and 66 placebo-recipients demonstrated an estimated efficacy 85% against amino acids mismatching at site 317 (p=0.004) 52% matching 307 (p=0.004). This supported data...
Background The gut mucosal homing integrin receptor α4β7 present on activated CD4+ T cells interacts with the HIV-1 gp120 second variable loop (V2). Case control analysis of RV144 phase III vaccine trial demonstrated that plasma IgG binding antibodies specific to scaffolded proteins expressing first and regions (V1V2) HIV envelope protein containing motif correlated inversely risk infection. Subsequently V3 region were also shown correlate protection. was interact LDI/V V2 but recent studies...
The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens, immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total subclass, IgA binding envelope (Env): gp120 proteins Cyclic V2 (CycV2) CycV3 peptides gp70 V1 scaffolds 3 trials. After two protein immunizations, IgG 92TH023 (contained...
We investigated the ability of N ‐octanoyl‐sphingosine (C 8 ‐Cer) stereoisomers, ‐octanoyl‐DL‐ erythro ‐dihydrosphingosine (DL‐ e ‐DHC ‐Cer), and a new ceramide derivative, ‐octyl‐D‐ ‐sphingosine (D‐ ‐C ‐Ceramine), to induce apoptosis in U937 cells. found C ‐Cer stereoisomers be stereo‐specific with D‐ L‐ threo being severalfold more potent than inducing nucleosomal fragmentation. The order potency was: t = > DL‐ ‐Cer. importance carbonyl group was by using ‐Ceramine, which replaced...
ABSTRACT Both a murine monoclonal antibody to phosphatidylinositol phosphate (PIP) and human (4E10) that is known have broadly neutralizing capabilities against primary isolates of immunodeficiency virus type 1 (HIV-1) bound PIP, as determined by enzyme-linked immunosorbent assay. Each the antibodies had antigen subsite binding specificities in aqueous medium for small phosphate-containing molecules inositol. The anti-PIP inhibited infection two HIV-1 neutralization assays employing...
The peptide segment of the second variable loop HIV-1 spanning positions 166–181 harbors two functionally important sites. first, 179–181, engages human α4β7 integrin receptor which is involved in T-cell gut-homing and may play a role immunodeficiency virus (HIV)-host cell interactions. second, at 166–178, major target anti-V2 antibodies elicited by ALVAC/AIDSVAX vaccine used RV144 clinical trial. Notably, these sites are directly adjacent, but do not overlap. Here, we report identity...
Human adenoviruses (AdV) are mostly associated with minimal pathology. However, more severe respiratory tract infections and acute diseases, most often caused by AdV-4 AdV-7, have been reported. The only licensed vaccine in the United States, live oral AdV-7 vaccine, is indicated for use military, nearly exclusively recruit populations. excellent safety profile prominent antibody response of well established placebo-controlled clinical trials, while, long-term immunity vaccination has not...
The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates decreased infection risk. New strategies to increase magnitude and durability protective immunity are critically needed. RV305 clinical trial evaluated immunological impact a follow-up boost HIV-1-uninfected RV144 recipients after 6–8 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 or ALVAC-HIV + gp120)....
Sexual transmission is the principal driver of human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against infections but samples were not collected, therefore, contribution antibodies to preventing HIV-1 acquisition unknown. Here, we report generation,...