A5054535186- Transgenic Plants and Applications
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Plant Virus Research Studies
- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Viral Infections and Outbreaks Research
- Plant tissue culture and regeneration
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- Bacillus and Francisella bacterial research
- Cytomegalovirus and herpesvirus research
- Immune responses and vaccinations
- IL-33, ST2, and ILC Pathways
- Inflammatory Bowel Disease
- vaccines and immunoinformatics approaches
- Innovation and Socioeconomic Development
- interferon and immune responses
- Respiratory viral infections research
Scripps (United States)
2022-2024
Scripps Research Institute
2020-2024
Scripps Institution of Oceanography
2022-2024
Arizona State University
2013-2019
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled cohort of severe acute respiratory syndrome 2 (SARS-CoV-2)-recovered participants, developed neutralization assays investigate antibody responses, adapted our high-throughput generation pipeline rapidly screen more than 1800 antibodies, established an animal model test protection. isolated potent neutralizing antibodies (nAbs) two epitopes on the receptor binding domain (RBD)...
Mammalian cell culture is the major platform for commercial production of human vaccines and therapeutic proteins. However, it cannot meet increasing worldwide demand pharmaceuticals due to its limited scalability high cost. Plants have shown be one most promising alternative pharmaceutical platforms that are robust, scalable, low-cost safe. The recent development virus-based vectors has allowed rapid high-level transient expression recombinant proteins in plants. To further optimize utility...
Current human biologics are most commonly produced by mammalian cell culture-based fermentation technologies. However, its limited scalability and high cost prevent this platform from meeting the ever increasing global demand. Plants offer a novel alternative system for production of pharmaceutical proteins that is more scalable, cost-effective, safer than current expression paradigms. The recent development deconstructed virus-based vectors has allowed rapid high-level transient recombinant...
The development of vaccines and therapeutics that are broadly effective against known emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires COVID-19 survivors vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing expansive view SARS-CoV-2-specific Ab repertoire. Among recovered was TXG-0078, N-terminal domain (NTD)-specific neutralizing mAb recognizes diverse alpha-...
The global Zika virus (ZIKV) outbreak and its link to foetal newborn microcephaly severe neurological complications in adults call for the urgent development of ZIKV vaccines. In response, we developed a subunit vaccine based on envelope (E) protein investigated immunogenicity mice. Transient expression E (zE) resulted rapid accumulation leaves Nicotiana benthamiana plants. Biochemical analysis revealed that plant-produced (PzE) exhibited specific binding panel monoclonal antibodies...
ABSTRACT The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled cohort SARS-CoV-2-recovered participants, developed neutralization assays interrogate serum monoclonal antibody responses, adapted our high throughput isolation, production characterization pipeline rapidly screen over 1000 antigen-specific antibodies, established an animal model test protection. We report multiple highly potent neutralizing antibodies (nAbs)...
Ulcerative colitis (UC) represents an inflammatory condition of the human colon believed in part to be mediated by dysregulation host immune system including potentially inadequate mucosal regulatory T-cell (Treg) responses.1Chang J.T. N Engl J Med. 2020; 383: 2652-2664Crossref PubMed Scopus (445) Google Scholar,2Laukova M. Glatman Zaretsky A. Eur Immunol. 2023; 53e2250007Crossref (8) Scholar Low-dose (LD) interleukin 2 (IL2) has been shown expand peripheral Tregs and ameliorate various...
Previously, our group engineered a plant-derived monoclonal antibody (MAb pE16) that efficiently treated West Nile virus (WNV) infection in mice. In this study, we developed pE16 variant consisting of single-chain variable fragment (scFv) fused to the heavy chain constant domains (CH) human IgG (pE16scFv-CH). and pE16scFv-CH were expressed assembled Nicotiana benthamiana ∆XF plants, glycosylation mutant lacking plant-specific N-glycan residues. Glycan analysis revealed (∆XFpE16scFv-CH)...
The mAb E60 has the potential to be a desirable therapeutic molecule since it efficiently neutralizes all four serotypes of dengue virus (DENV). However, mammalian-cell-produced exhibits antibody-dependent enhancement infection (ADE) activity, rendering inefficacious in vivo, and treated animals more susceptible developing severe diseases during secondary infection. In this study, we evaluated plant-based expression system for production therapeutically suitable E60. was transiently...
Summary Chikungunya virus ( CHIKV ) is a mosquito‐transmitted alphavirus, and its infection can cause long‐term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat infections. In this study, we explored the feasibility of using an anti‐ monoclonal antibody mA b) produced wild‐type WT glycoengineered (∆ XFT Nicotiana benthamiana plants treating mouse model. b was efficiently expressed assembled plant leaves enriched homogeneity...
Lassa fever is an acute hemorrhagic caused by the zoonotic virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and sole target for neutralizing antibodies. Immunogen design complicated metastable nature of recombinant GPCs antigenic differences among phylogenetically distinct lineages. Despite sequence diversity GPC, structures most lineages are lacking. We present development characterization prefusion-stabilized, trimeric II, V, VII, revealing structural conservation...
A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted AS01
Mammalian cell culture is the major platform for commercial production of human vaccines and therapeutic proteins. However, it cannot meet increasing worldwide demand pharmaceuticals due to its limited scalability high cost. Plants have shown be one most promising alternative pharmaceutical platforms that are robust, scalable, low-cost safe. The recent development virus-based vectors has allowed rapid high-level transient expression recombinant proteins in plants. To further optimize utility...
We described the rapid production of domain III (DIII) envelope (E) protein in plants as a vaccine candidate for West Nile Virus (WNV). Using various combinations vector modules deconstructed viral expression system, DIII was produced three subcellular compartments leaves Nicotiana benthamiana by transient expression. expressed at much higher levels when targeted to endoplasmic reticulum (ER) than that chloroplast or cytosol, with accumulation level up 73 μ g per gram leaf fresh weight...
The ability to efficiently isolate antigen-specific B cells in high throughput will greatly accelerate the discovery of therapeutic monoclonal antibodies (mAbs) and catalyze rational vaccine development. Traditional mAb is a costly labor-intensive process, although recent advances single-cell genomics using emulsion microfluidics allow simultaneous processing thousands individual cells. Here we present streamlined method for isolation analysis large numbers cells, including next generation...
ABSTRACT The ability to efficiently isolate antigen-specific B cells in high throughput will greatly accelerate the discovery of therapeutic monoclonal antibodies ( mAbs ) and catalyze rational vaccine development. Traditional mAb is a costly labor-intensive process, although recent advances single-cell genomics using emulsion microfluidics allow simultaneous processing thousands individual cells. Here we present streamlined method for isolation analysis large numbers cells, including next...
Abstract The emergence of the novel coronavirus, SARS-CoV-2, during COVID-19 pandemic prompted investigations into pre-existing immunity in human populations. Despite being a new individuals had previous exposure to common seasonal coronaviruses. In this study, we examined SARS-CoV-2-specific memory B cells six pre-pandemic Lassa virus-infected patients from West Africa. By incorporating SARS-CoV-2 Spike Antigen (WA-1 strain) broader antigen panel that included virus GPC and control,...
Lassa virus (LASV), an arenavirus endemic to West Africa, poses a significant public health threat due its high pathogenicity and expanding geographic risk zone. LASV glycoprotein complex (GPC) is the only known target of neutralizing antibodies, but inherent metastability conformational flexibility have hindered development GPC-based vaccines. We employed variant AlphaFold2 (AF2), called subsampled AF2, generate diverse structures GPC that capture array potential states using MSA...
Abstract/Summary During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral with host cell. As such, FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe vaccination study non-human primates (NHPs) where glycan deletions were made on soluble Env to increase exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against FP, which then boosted heterologous...
Summary Development of vaccines and therapeutics that are broadly effective against known emergent coronaviruses is an urgent priority. Current strategies for developing pan-coronavirus countermeasures have largely focused on the receptor binding domain ( RBD ) S2 regions coronavirus Spike protein; it has been unclear whether N-terminal NTD a viable target universal neutralizing antibodies Abs ). Additionally, many RBD-targeting proven susceptible to viral escape. We screened circulating B...
Abstract Background A significant proportion of patients with ulcerative colitis (UC) have suboptimal responses to medical therapy. Expansion regulatory T cells (Tregs), but not conventional (Tcons), through the use low doses (LD) cell growth factor Interleukin-2 (IL-2, Proleukin®), has been a promising approach in other immune-mediated diseases and pre-clinical humanized UC mouse models. We performed phase 1b/2a clinical trial moderate-to-severe determine if subcutaneously (SC) administered...
Summary Lassa fever is an acute hemorrhagic caused by the zoonotic virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and sole target for neutralizing antibodies. Immunogen design complicated metastable nature of recombinant GPCs antigenic differences amongst lineages. Despite sequence diversity GPC, structures most lineages are lacking. We present development characterization prefusion-stabilized, trimeric II, V, VI, revealing structural conservation despite diversity....