William C. Chang
A5029808837- SARS-CoV-2 and COVID-19 Research
- COVID-19 Impact on Reproduction
- COVID-19 Clinical Research Studies
- Cancer Treatment and Pharmacology
- Animal Virus Infections Studies
- Blood Coagulation and Thrombosis Mechanisms
- 14-3-3 protein interactions
- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Hemophilia Treatment and Research
- SARS-CoV-2 detection and testing
- Microtubule and mitosis dynamics
- Venous Thromboembolism Diagnosis and Management
- Adenosine and Purinergic Signaling
- Platelet Disorders and Treatments
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- HER2/EGFR in Cancer Research
- Hepatitis B Virus Studies
- Herpesvirus Infections and Treatments
- Macrophage Migration Inhibitory Factor
- Calcium signaling and nucleotide metabolism
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- HIV Research and Treatment
- Protein Tyrosine Phosphatases
Henry M. Jackson Foundation
2021-2024
Walter Reed Army Institute of Research
2021-2024
Center for Biologics Evaluation and Research
2015-2023
United States Food and Drug Administration
2015-2023
University of California, Davis
2022-2023
University of Utah
2016
Colorado School of Mines
2016
Yale University
2008-2015
Dartmouth College
2012
Royal College of Physicians and Surgeons of Glasgow
2005
The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants concern (VoCs) and long-term threat emerging coronaviruses. Here, we design characterize four categories engineered nanoparticle immunogens that recapitulate structural antigenic properties prefusion SARS-CoV-2 spike (S), S1, receptor-binding domain (RBD). These induce robust S binding, ACE2 inhibition, authentic pseudovirus neutralizing antibodies...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T H 1)–biased CD4 response elicited neutralizing antibodies wild type concern, as well SARS-CoV-1....
Abstract The emergence of variants concern, some with reduced susceptibility to COVID-19 vaccines underscores consideration for the understanding vaccine design that optimizes induction effective cellular and humoral immune responses. We assessed a SARS-CoV-2 spike-ferritin nanoparticle (SpFN) immunogen paired two distinct adjuvants, Alhydrogel ® or Army Liposome Formulation containing QS-21 (ALFQ) unique evoked signatures. Recruitment highly activated multifaceted antigen-presenting cells...
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...
Despite rapid and ongoing vaccine therapeutic development, SARS-CoV-2 continues to evolve evade, presenting a need for next-generation diverse modalities. Here we show that nurse sharks immunized with recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit set of new antigen antibody (IgNAR) molecules target two non-overlapping conserved epitopes on the RBD. Representative shark variable NAR-Fc chimeras (ShAbs) targeting...
Abstract The repeat emergence of SARS-CoV-2 variants concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need develop next-generation vaccine candidates that confer broad protection. Here we describe antibody response induced by Spike Ferritin Nanoparticle (SpFN) candidate adjuvanted Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal directed against Receptor Binding Domain (RBD),...
Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites vulnerability on the spike glycoprotein. Here we identify several potent neutralizing directed either N-terminal domain (NTD) or receptor-binding (RBD) protein. Administered in combinations, these mAbs provided low-dose protection SARS-CoV-2 infection K18-human angiotensin-converting...
Characterization of MAbs against SARS-CoV-2, elicited through vaccination or natural infection, has provided vital immunotherapeutic options for curbing the COVID-19 pandemic and supplied critical insights into SARS-CoV-2 escape, transmissibility, mechanisms viral inactivation. Neutralizing that target RBD but do not block ACE2 binding are particular interest because epitopes well conserved within sarbecoviruses targeting this area demonstrate cross-reactivity.
The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) been rapid. However, novel strategies are still necessary to slow the pandemic, this includes new approaches vaccine and/or delivery that will improve vaccination compliance demonstrate efficacy emerging variants. Here, we report immunogenicity comprising stabilized, pre-fusion spike protein trimers...
Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VoCs), immunotherapeutics that target conserved epitopes on spike (S) glycoprotein have therapeutic advantages. Here, we report crystal structure SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility distinct conformations angiotensin-converting enzyme (ACE2)-binding site. We identify a set SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD...
Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates myriad biological activities, including angiogenesis and promotion cell growth, survival, differentiation through production lysophosphatidic acid (LPA). ATX increases aggressiveness invasiveness transformed cells, levels directly correlate with tumor stage grade in several malignancies. To study role pathogenesis malignant melanoma, we developed antibodies...
This study demonstrates the impact of adjuvant on development T follicular helper (Tfh) and B cells, their influence antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel
The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 µ g) SpFN vaccine, given twice within a 28 day interval, induced Th1-biased CD4 T cell helper response peak neutralizing antibody geometric mean...
Despite the availability of currently approved antiviral drugs, infections with human cytomegalovirus (HCMV) still cause clinically challenging, sometimes life-threatening situations. There is an urgent need for enhanced anti-HCMV drugs that offer improved efficacy, reduced dosages and options long-term treatment without risk development viral drug resistance. Recently, we reported pronounced efficacy pharmacological inhibitors cyclin-dependent kinases (CDKs), in particular, potential...
Autotaxin (ATX) is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), initiating signaling cascades leading to cancer metastasis, wound healing, and angiogenesis. Knowledge of the pathway kinetics LPA synthesis by ATX critical for developing quantitative physiological models signaling. We measured individual rate constants synthase cycle using fluorescent lipid substrates FS-3 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-LPC....
SUMMARY The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants concern (VoC) and long-term threat other coronaviruses. Here, we designed characterized four categories engineered nanoparticle immunogens that recapitulate structural antigenic properties prefusion Spike (S), S1 RBD. These induced robust S-binding, ACE2-inhibition, authentic pseudovirus neutralizing antibodies against in mice. A Spike-ferritin (SpFN) vaccine elicited titers more than...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines demonstrate reduced protection against acquisition of BA.5 subvariant but are still effective severe disease. However, immune correlates remain unknown. We report the immunogenicity and protective efficacy vaccine regimens consisting vector-based Ad26.COV2.S adjuvanted spike ferritin nanoparticle (SpFN) a high-dose, mismatched Omicron challenge in macaques. The SpFNx3 Ad26 + SpFNx2 elicit higher antibody responses than...
Objective— Recent evidence suggests involvement of coagulation factor XIa (FXIa) in thrombotic event development. This study was conducted to explore possible synergies between tissue (TF) and exogenous FXIa (E-FXIa) thrombin generation. Approach Results— In generation assays, for increasing concentrations E-FXIa with low, but not high TF concentrations, peak significantly increased whereas lag time decreased. Similar dependencies times rates were found mathematical model simulations. both...
ABSTRACT 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...
Abstract Potent cellular responses to viral infections are pivotal for long -lived protection. Evidence is growing that these critical in SARS -CoV-2 immunity. Assessment of a spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel® (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment highly activated classical and non -classical antigen presenting cells (APCs) the...
The rapid emergence of SARS-CoV-2 variants concern (VoC) and the threat future zoonotic sarbecovirus spillover emphasizes need for broadly protective next-generation vaccines therapeutics. We utilized spike ferritin nanoparticle (SpFN), receptor binding domain (RFN) immunogens, in an equine model to elicit hyperimmune sera evaluated its neutralization protection capacity. Immunized animals rapidly elicited with potent VoC, SARS-CoV-1 pseudoviruses, against domains from clades 1b, 1a, 2, 3,...
Reliable and reproducible monitoring of the conformational state therapeutic protein products remains an unmet technological need. This need is amplified by increasing number biosimilars entering drug development pipeline as many branded biologics are reaching end their market exclusivity period. Availability methods to better characterize conformation may improve detection counterfit unlicensed proteins. In this study, we report use a set modified DNA aptamers with enhanced chemical...