A5017149387- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Cancer-related molecular mechanisms research
- Biochemical and Structural Characterization
- Animal Virus Infections Studies
- Angiogenesis and VEGF in Cancer
- Glycosylation and Glycoproteins Research
- Circular RNAs in diseases
- HIV/AIDS Research and Interventions
- RNA modifications and cancer
- vaccines and immunoinformatics approaches
- Polyomavirus and related diseases
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- Cytomegalovirus and herpesvirus research
- Genomic variations and chromosomal abnormalities
California Institute of Technology
2018-2024
University of California, Berkeley
2023-2024
Central South University
2022
Xiangya Hospital Central South University
2022
Zhejiang University
2021
Jiangxi Provincial Academy of Medical Sciences
2016
Nanchang University
2016
National Institute of Allergy and Infectious Diseases
2012-2015
National Institutes of Health
2012-2015
Affiliated Hospital of Chengde Medical College
2013
Here we report on the antibody and memory B cell responses of a cohort 20 volunteers who received Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine against SARS-CoV-21-4. Eight weeks after second injection vaccine, showed high levels IgM IgG anti-SARS-CoV-2 spike protein (S) receptor-binding-domain (RBD) binding titre. Moreover, plasma neutralizing activity relative numbers RBD-specific cells vaccinated were equivalent to those individuals had recovered from natural infection5,6....
To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in two deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including novel mRNA-based 1,2 . These elicit neutralizing antibodies and appear be safe effective, but the precise nature of elicited is not known 3–6 Here we report on antibody memory B cell responses a cohort 20 volunteers who received either Moderna (mRNA-1273) or...
Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain levels. We present a natural infection-mimicking technology that combines features of mRNA- protein nanoparticle-based through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins induce...
DNA can be introduced into a variety of cell types after formation liposomal complexes with cationic lipids. In this report, conditions have been established to optimize the production DNA-liposome that efficiently transfect cells. The safety and toxicity method gene delivery assessed in vivo administration, either by intravenous or direct intratumor injection. Nine eleven days injection, was found primarily heart lung tissue PCR analysis. No abnormalities were evident from histologic...
Platelet-derived growth factor (PDGF) B chain induces cell proliferation in vitro and is associated with arterial lesions that cause cardiovascular disease. However, it has been difficult to document the biological response PDGF gene expression arteries vivo. To determine biologic effects of this vivo, we have introduced an eukaryotic vector plasmid encoding recombinant by direct transfer into porcine iliofemoral using DNA liposome complexes. The presence mRNA were confirmed polymerase...
The resistance of acquired immunodeficiency syndrome (AIDS) to traditional drug therapy has prompted a search for alternative treatments this disease. One potential approach is provide genetic viral replication prolong latency. This strategy requires the definition effective antiviral genes that extend survival T cells in human virus (HIV)-infected individuals. We report results study designed determine whether intervention can HIV-infected Gene transfer was performed enriched CD4+ with...
HIV-1 Env, a trimer of gp120-gp41 heterodimers, mediates membrane fusion after binding host receptor CD4. Receptor displaces V1V2 loops from Env's apex, allowing coreceptor and opening Env to enable gp41-mediated fusion. We present 3.54 Å 4.06 cryoelectron microscopy structures partially open soluble native-like trimers (SOSIPs) bound One structure, complex with coreceptor-mimicking antibody that binds both CD4 gp120, stabilizes the displaced reveals its structure. Comparing fully Envs...
Abstract Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. We develop software tool, Variant Database (VDB), for quickly examining changing landscape of spike mutations. Using VDB, we detect an emerging lineage in New York region that shares mutations with previously reported variants. The most common sets this (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This was first sequenced late November...
Abstract Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. Variants first detected in United Kingdom, South Africa, and Brazil have spread multiple countries. We developed software tool, Variant Database (VDB), for quickly examining changing landscape of spike mutations. Using VDB, we an emerging lineage New York region that shares mutations with previously reported variants. The most common sets this (now designated as B.1.526) are...
Current influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral response conserved regions on antigens are therefore required for recognition by neutralizing antibodies. It has been suggested that B-cells with receptors recognize epitopes would be preferentially stimulated through avidity effects mosaic particles presenting forms of a variable antigen. We adapted SpyCatcher-based platforms, AP205 virus-like (VLPs) and...
The potency and breadth of the recently isolated neutralizing human monoclonal antibodies to HIV-1 have stimulated interest in their use prevent or treat infection. Due antigenically diverse nature envelope (Env), no single antibody is highly active against all viral strains. While physical combination two broadly (bNAbs) can improve coverage majority viruses, clinical-grade manufacturing testing independent products are time resource intensive. In this study, we constructed bispecific...
Fusion of HIV-1 with the membrane its target cell, an obligate first step in virus infectivity, is mediated by binding viral envelope (Env) spike protein to receptors, CD4 and CCR5/CXCR4, on cell surface. The process fusion appears be fast compared egress has not been visualized EM. To capture events, must curtailed trapping Env-receptor at intermediate stage. We have used inhibitors trap virions attached cells Envs extended pre-hairpin state. Electron tomography revealed bound TZM-bl 2-4...
Sequential immunization elicits antibodies against the V3-glycan patch of HIV-1 Env in rhesus macaques and also induces off-target antibody responses.
Abstract Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both recognize CD4bs on trimer with an ‘occluded-open’ conformation between as targeted by bNAbs, fully-open,...
Abstract HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120 and gp41 heterodimers, has been structurally characterized closed, prefusion conformation with closely associated gp120s coreceptor binding sites on V3 hidden by V1V2 loops 1–4 fully saturated CD4-bound open Env conformations including outwardly rotated displaced 3–9 . To investigate resulting from substoichiometric CD4 binding, we solved...
Passive transfer of broadly neutralizing anti–HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal HIV-1 vaccine efforts. that target the CD4 binding site (CD4bs) on Env are among most active, but to date, responses elicited this epitope in vaccinated animals have lacked potency breadth. We hypothesized CD4bs resembling antibody IOMA might be easier elicit than other exhibit higher somatic mutation rates, difficult-to-achieve...
The study and treatment of pulmonary diseases may be greatly facilitated by in vivo expression specific recombinant genes the vasculature lung parenchyma. To evaluate feasibility gene transfer to vasculature, cationic liposomes adenoviral vectors encoding a human placental alkaline phosphatase (hpAP) were delivered into artery 24 pigs percutaneous right heart catheterization. Pulmonary tissue was harvested within 20 minutes or 5, 14, 28 days later analyzed for expression. Five after exposure...
Significance The ability of HIV-1 to rapidly develop resistance against various therapeutics remains a roadblock finding cure. Here we propose that nanoparticle-based mimic target cells by presenting clusters CD4, the receptor, could prevent effective viral escape. We show CD4 multimerization on nanoparticle dramatically enhanced neutralization potency and breadth compared with conventional CD4-based reagents present only one or two copies CD4. nanoparticles neutralized range diverse...
A new retrovirus vector containing the gene for hygromycin B resistance (hyg) as a selectable marker under control of an internal simian virus 40 promoter was constructed. It used, together with analogous previously described vector, DO1, which contains G418 resistance, to introduce and express genes two chains human class II major histocompatibility complex antigen in NIH 3T3 cells. In addition, these vectors were used DR antigens mutant B-lymphoblastoid cell lines, one deleted both alleles...
A potential non-viral gene-transfer vector, poly(ethylenimine)-grafted-poly[(aspartic acid)-co-lysine] (PSL), has been developed by thermal polycondensation of aspartic acid and lysine under reduced pressure. Low-molecular-mass branch poly(ethylenimine) (PEI600) was conjugated to the backbone. The chemical structure resulting co-polymer identified H-NMR, FT-IR, TGA X-ray diffraction. results MTT assay showed that at concentration up 4000 nmol/l vector cell viability over 80% low toxicity....