Johnathan D. Guest
A5025301084- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Protein Structure and Dynamics
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Machine Learning in Bioinformatics
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Chronic Lymphocytic Leukemia Research
- Malaria Research and Control
- Animal Virus Infections Studies
- Machine Learning in Materials Science
- Cytomegalovirus and herpesvirus research
- Photography and Visual Culture
- Bioinformatics and Genomic Networks
- COVID-19 Clinical Research Studies
Institute for Bioscience and Biotechnology Research
2018-2025
University of Maryland, College Park
2018-2025
Advanced Bioscience Laboratories (United States)
2018-2025
AstraZeneca (United States)
2023-2024
Research Institute for Bioscience and Biotechnology
2023
National Institute of Standards and Technology
2018-2022
University of Maryland, Baltimore
2018-2022
Integral Molecular (United States)
2017
Abstract We present the results for CAPRI Round 54, 5th joint CASP‐CAPRI protein assembly prediction challenge. The offered 37 targets, including 14 homodimers, 3 homo‐trimers, 13 heterodimers antibody–antigen complexes, and 7 large assemblies. On average ~70 CASP predictor groups, more than 20 automatics servers, submitted models each target. A total of 21 941 by these groups 15 scorer were evaluated using model quality measures DockQ score consolidating measures. performance was quantified...
We present the results for CAPRI Round 46, third joint CASP-CAPRI protein assembly prediction challenge. The comprised a total of 20 targets including 14 homo-oligomers and 6 heterocomplexes. Eight homo-oligomer one heterodimer proteins that could be readily modeled using templates from Protein Data Bank, often available full assembly. remaining 11 5 homodimers, 3 heterodimers, two higher-order assemblies. These were more difficult to model, as their mainly involved "ab-initio" docking...
Abstract We present the results for CAPRI Round 50, fourth joint CASP‐CAPRI protein assembly prediction challenge. The comprised a total of twelve targets, including six dimers, three trimers, and higher‐order oligomers. Four these were easy which good structural templates available either full assembly, or main interfaces (of oligomers). Eight difficult targets only distantly related found individual subunits. Twenty‐five groups eight automatic servers submitted ~1250 models per target....
Abstract SARS-CoV-2, the etiologic agent of COVID-19, exemplifies general threat to global health posed by coronaviruses. The urgent need for effective vaccines and therapies is leading a rapid rise in number high resolution structures SARS-CoV-2 proteins that collectively reveal map virus vulnerabilities. To assist structure-based design therapeutics against other coronaviruses, we have developed CoV3D, database resource coronavirus protein structures, which updated on weekly basis. CoV3D...
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from infections were subtyped, sequenced analyzed for binding site substitutions; subsequently, recombinant RSVs engineered microneutralization susceptibility testing. Here we show frequency caused...
The development of a prophylactic vaccine for hepatitis C virus (HCV) remains global health challenge. Cumulative evidence supports the importance antibodies targeting HCV E2 envelope glycoprotein to facilitate viral clearance. However, significant challenge B cell-based is focusing immune response on conserved epitopes capable eliciting neutralizing not associated with escape. We hypothesized that glycosylation might influence antigenicity and immunogenicity E2. Accordingly, we performed...
The hepatitis C virus (HCV) envelope glycoproteins E1 and E2 form a non-covalently linked heterodimer on the viral surface that mediates entry. E1, complex E1E2 are candidate vaccine antigens, but technically challenging to study because of difficulties in producing natively folded proteins by standard protein expression purification methods. To better comprehend antigenicity these proteins, library alanine scanning mutants comprising entirety (555 residues) was created for evaluating role...
T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide-MHC targets lacking. Here we determine the structures of public private TCR from COVID-19 convalescent patients complex with HLA-A2 two spike protein epitopes (YLQ RLQ). The reveal basis for selection particular TRAV TRBV germline...
ABSTRACT Accurate modeling of the structures protein–protein complexes and other biomolecular interactions represents a longstanding important challenge for computational biology. The Critical Assessment PRedicted Interactions (CAPRI) experiment has served over two decades as key means to assess compare current approaches methods through blind predictive scenarios, highlighting useful strategies, new developments. Here we describe performance our laboratory's team in recent CAPRI rounds,...
Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of B cell response associated with is crucial inform vaccine design. From an individual who cleared three sequential HCV infections genotypes 1b, 1a 3a strains, respectively, we employed peripheral cells isolate characterize human monoclonal (HMAbs) after genotype 1 infections. The majority...
Therapeutic anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (MAbs) provide immunosuppressed and vulnerable populations with prophylactic treatment interventions against disease 2019 (COVID-19). AZD7442 (tixagevimab-cilgavimab) is a combination of extended-half-life neutralizing MAbs that bind to distinct epitopes on the receptor binding domain (RBD) SARS-CoV-2 spike protein. The Omicron variant concern carries mutations at >35 positions in protein has...
Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement neutralizing breadth vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic antigenic diversity circulating strains, lack standardization these makes it difficult to compare neutralization results obtained in different studies. Here, we describe selection validation genetically antigenically diverse reference panel 15 pseudoparticles...
Abstract Hepatitis C virus (HCV) is a major global health burden as the leading causative agent of chronic liver disease and hepatocellular carcinoma. While main antigenic target for HCV-neutralizing antibodies membrane-associated E1E2 surface glycoprotein, development effective vaccines has been hindered by complications in biochemical preparation soluble ectodomains. Here, we present cryo-EM structure an engineered, secreted ectodomain genotype 1b complex with neutralizing AR4A, HEPC74,...
Significance Hepatitis C virus infects 1% of the world’s population, with no vaccine currently available. One candidate is membrane-associated E1E2 envelope glycoprotein which has been used in clinical studies. However, a major challenge to both structural studies and rational design high-yield production homogenous E1E2. Production liberated from membrane native structure antigenicity would thus represent advance. We describe validation soluble, secreted (sE1E2) antigen scaffold replaces...
An effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens modulate the structure dynamics E2 favor induction broadly neutralizing (bNAbs) in context vaccine. These designs include point mutation antigenic site stabilize its conformation, as well redesigns immunogenic region add new N-glycosylation...
Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials "first-generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" will be required for optimal clinical utility, while preserving enhancing Current Good Manufacturing Practices (cGMP)...
Significance Hepatitis C virus chronically infects approximately 1% of the world’s population, making an effective vaccine for hepatitis a major unmet public health need. The membrane-associated E1E2 envelope glycoprotein has been used in clinical studies as candidate. However, limited neutralization breadth and difficulty producing large amounts homogeneous have hampered efforts to develop E1E2-based vaccine. Our previous work described design biochemical validation native-like soluble...
The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by emergence and spread variants, including Alpha (B.1.1.7) Delta (B.1.617.2), some which appear to be less effectively targeted current monoclonal antibodies vaccines. Here we report high resolution comprehensive map recognition spike receptor binding domain (RBD), target most neutralizing antibodies, using computational structural analysis. With dataset...
We present the results for CAPRI Round 54, 5th joint CASP-CAPRI protein assembly prediction challenge. The offered 37 targets, including 14 homo-dimers, 3 homo-trimers, 13 hetero-dimers antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP predictor groups, more than 20 automatics servers, submitted models each target. A total of 21941 by these groups 15 scorer were evaluated using model quality measures DockQ score consolidating measures. performance was quantified a...
Accurate predictive modeling of antibody-antigen complex structures and structure-based antibody design remain major challenges in computational biology, with implications biotherapeutics, immunity, vaccines. Through a systematic search for high resolution complexes unbound antigen structures, conjunction identification experimentally determined binding affinities, we have assembled non-redundant set test cases docking affinity prediction. This benchmark more than doubles the number...