Geoffrey B. Hutchinson
A5051128983- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Influenza Virus Research Studies
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- HIV Research and Treatment
- Viral Infections and Outbreaks Research
- Viral gastroenteritis research and epidemiology
- Virology and Viral Diseases
- Biochemical and Structural Characterization
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Economic Theory and Policy
- Virus-based gene therapy research
- Law, logistics, and international trade
- SARS-CoV-2 detection and testing
- Inhalation and Respiratory Drug Delivery
- Nanoplatforms for cancer theranostics
- Brucella: diagnosis, epidemiology, treatment
- Animal Virus Infections Studies
- Political Economy and Marxism
- Maritime Security and History
- International Maritime Law Issues
National Institute of Allergy and Infectious Diseases
2020-2023
National Institutes of Health
2020-2023
University of Washington
2022
Centers for Disease Control and Prevention
2020
Riverside University Health System - Medical Center
2020
Synergy America (United States)
2020
Rhode Island Department of Health
2020
Providence College
2020
Multivalent presentation of viral glycoproteins can substantially increase the elicitation antigen-specific antibodies. To enable a new generation anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present ectodomains influenza, HIV, and RSV glycoprotein trimers. We first de novo trimers for antigen fusion, featuring N-terminal helices positioned match C termini glycoproteins. Trimers that experimentally adopted their configurations were...
Summary A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed application of prefusion-stabilizing mutations that improved expression and immunogenicity betacoronavirus spike proteins. Using this established immunogen design, release sequences triggered immediate rapid manufacturing an mRNA expressing prefusion-stabilized trimer (mRNA-1273). Here, we show mRNA-1273 induces both potent neutralizing antibody CD8 T cell responses...
Abstract Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies their production. To alleviate this issue, we developed a plug-and-play platform using spontaneous isopeptide-bond formation SpyTag:SpyCatcher system to display trimeric antigens nanoparticles, including 60-subunit Aquifex aeolicus...
Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, calculate the burden disease and case fatality rates. Molecular diagnostics, gold standard for identifying viremic cases, are not ideal determining true counts rates asymptomatic infection. Serological detection specific antibodies can contribute filling these knowledge gaps. In this study, we describe optimization validation SARS-CoV-2-specific-enzyme linked...
Licensed vaccines or therapeutics are rarely available for pathogens with epidemic pandemic potential. Developing interventions specific and defining generalizable approaches related is a global priority inherent to the UN Sustainable Development Goals. Nipah virus (NiV) poses significant threat, zoonotic transmission from bats-to-humans high fatality rates occurs almost annually. Human-to-human of NiV has been documented in recent outbreaks leading public health officials government...
Abstract The conserved hemagglutinin (HA) stem has been a focus of universal influenza vaccine efforts. Influenza A group 1 HA stem-nanoparticles have demonstrated to confer heterosubtypic protection in animals; however, the does not extend 2 viruses, due part differences glycosylation between and stems. Here, we show that introducing glycan at Asn38 HA1 stem-nanoparticle (gN38 variant) based on A/New Caledonia/20/99 (H1N1) broadens antibody responses cross-react with HAs. Immunoglobulins...
Nipah virus (NiV) represents a significant pandemic threat with zoonotic transmission from bats-to-humans almost annual regional outbreaks characterized by documented human-to-human and high fatality rates. Currently, no vaccine against NiV has been approved. Structure-based design protein engineering principles were applied to stabilize the fusion (F) in its prefusion trimeric conformation (pre-F) improve expression increase immunogenicity. We covalently linked stabilized pre-F through...
Abstract Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains notably mutable viruses. In coronaviruses, this work predominantly aimed at targeting conserved epitopes receptor binding domain. However, non-RBD could limit potential for antigenic escape. To explore new targets, we engineered protein nanoparticles...
Abstract Influenza vaccines that confer broad and durable protection against diverse virus strains would have a major impact on global health. However, next-generation vaccine design efforts been complicated by challenges including the genetic plasticity of immunodominance certain epitopes in its glycoprotein antigens. Here we show computationally designed, two-component nanoparticle immunogens induce potently neutralizing broadly protective antibody responses wide variety influenza viruses....
Immunogen design approaches aim to control the specificity and quality of antibody responses elicited by next-generation vaccines. Here, we use computational protein generate a nanoparticle vaccine platform based on receptor-binding domain (RBD) influenza hemagglutinin (HA) that enables precise antigen conformation spacing. HA RBDs are presented as either monomers or native-like closed trimers connected underlying rigid linker is modularly extended precisely Nanoparticle immunogens with...
Abstract Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies their production. To alleviate this issue, we developed a plug-and-play platform using spontaneous isopeptide-bond formation SpyTag:SpyCatcher system to display trimeric antigens nanoparticles, including 60-subunit Aquifex aeolicus...
Abstract The adaptive immune system is highly sensitive to arrayed antigens, and multivalent display of viral glycoproteins on symmetric scaffolds has been found substantially increase the elicitation antigen-specific antibodies. Motivated by considerable promise this strategy for next-generation anti-viral vaccines, we set out design new self-assembling protein nanoparticles with geometries specifically tailored scaffold ectodomains different glycoproteins. We first designed characterized...
To determine prevalence of, seroprevalence and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning the United States from Wuhan, China, in January 2020, we conducted cross-sectional study quarantined 1 repatriation flight. Overall, 193 195 completed surveys submitted upper or serum specimens both at arrival States. Nearly all had taken preventive measures limit while none detectable SARS-CoV-2 tract specimens, suggesting...
Multivalent antigen display is a fast-growing area of interest towards broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains notably mutable viruses. In coronaviruses, this work predominantly aimed at targeting conserved epitopes receptor-binding domain. However, other non-RBD could further limit potential for antigenic escape. To explore new targets, we engineered protein...