A5001371865- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Immunology Research
- Virus-based gene therapy research
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- Hepatitis Viruses Studies and Epidemiology
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
- Advanced Thermodynamic Systems and Engines
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Adenosine and Purinergic Signaling
- COVID-19 Impact on Reproduction
- Monoclonal and Polyclonal Antibodies Research
- Animal Disease Management and Epidemiology
- CAR-T cell therapy research
- Parvovirus B19 Infection Studies
- Congenital Diaphragmatic Hernia Studies
- Bacterial Infections and Vaccines
- Herpesvirus Infections and Treatments
- Clostridium difficile and Clostridium perfringens research
- Mosquito-borne diseases and control
- Nanoplatforms for cancer theranostics
University of North Carolina at Chapel Hill
2017-2025
Public Health Department
2017-2023
University of North Carolina Health Care
2022
Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates protection, moreover, remain poorly understood. Here, we report GII.4-serological antibody repertoire—pre- post-vaccination—and select several clonotypes for epitope structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or bound to...
<h3>Importance</h3> Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting. <h3>Objective</h3> To evaluate the immunogenicity durability of heterologous homologous prime-boost regimens involving adenovirus vector vaccine Ad26.COV2.S mRNA BNT162b2. <h3>Design, Setting, Participants</h3> In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated least 6 months previously with 2...
The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development countermeasures provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive...
Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design broadly protective immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics quantitatively characterize circulating serum IgG repertoire before after immunization with an experimental monovalent GII.4 VP1 capsid-encoding adenoviral vaccine....
The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications pediatric infections and limit transmission could possibly be implemented via global schedule. However, age-dependent differences immune function require careful evaluation novel vaccines population. Toward this goal, we assessed safety immunogenicity two vaccines. Two groups 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 4 with stabilized prefusion S-2P spike...
Significance Some coronaviruses utilize angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Although reducing agents, such as N -acetylcysteine, disrupt viral binding to ACE2 in general, these compounds are cytotoxic, have low potency, and because of their membrane permeability, undefined mechanism action. With qualitative chemoproteomic mapping delineate cysteine thiol/disulfide reactivity native spike recombinant receptor domain (RBD), we report nontoxic, cell-impermeable...
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants concern (VOCs) that replace ancestral strains. Here, we dissect complex selective pressures evaluating variant fitness and adaptation in human tissues. We evaluate viral properties host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. observe differential replication airway epithelia, differences cellular tropism, virus-induced cytotoxicity....
Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, persistent emergence acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VOCs) can evade vaccine-elicited immunity remains a global health concern. In addition, SARS-CoV-2 VOCs therapeutic monoclonal antibodies underscores need for additional, variant-resistant treatment strategies. Here, we characterize antiviral activity GS-5245, obeldesivir (ODV), an oral prodrug parent...
Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver pandemic emergence and significant obstacle to development cross-protective immunity after natural infection vaccination. However, mouse monoclonal antibody studies indicate that, although rare, antibodies conserved blockade epitopes are generated. The mechanisms by which these evade immune surveillance uncertain. Here, we developed new approach for identifying epitopes. Utilizing unique set...
In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree.
Immune responses to SARS-CoV-2 primarily target the receptor binding domain of spike protein, which continually mutates escape acquired immunity. Other regions in S2 subunit, such as stem helix and segment encompassing residues 815-823 adjacent fusion peptide, are highly conserved across sarbecoviruses recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current emergent viruses. Here we employ computational...
The control of re-occurring pandemic pathogens requires understanding the origins new variants and factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds millions annual gastroenteritis cases. Previous studies have hypothesized viruses arise when previously circulating or pre-pandemic undergo substitutions in antigenic regions enable evasion host population immunity, as described by...
The emergence of three highly pathogenic human coronaviruses—severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern (MERS)-CoV 2012, and SARS-CoV-2 2019—underlines the need to develop broadly active vaccines against Merbecovirus Sarbecovirus betacoronavirus subgenera. While protect severe COVID-19, they do not other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing SARS-CoV-2,...
Human norovirus is a significant public health burden, with >30 genotypes causing endemic levels of disease and strains from the GII.4 genotype serial pandemics as virus evolves new ligand binding antigenicity features. During 2014–2015, GII.17 cluster IIIb emerged leading cause infection in select global locations. Comparison capsid sequences indicates that evolving at previously defined antibody epitopes. Antigenicity virus-like particles (VLPs) representative clusters I, II, were compared...
Human noroviruses are the leading cause of acute gastroenteritis. Strains GII.4 genotype pandemic waves associated with viral evolution and subsequent antigenic drift ligand-binding modulation. In November 2015, a novel Sydney recombinant variant (GII.P16-GII.4 Sydney) emerged replaced GII.Pe-GII.4 as predominant gastroenteritis in 2016-2017 season United States.Virus-like particles 2012 2015 were compared for ligand binding antibody reactivity, using surrogate neutralization assay.Residue...
Background & AimsHuman norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2-/-) limited array HBGAs. Thus, have less infections, including resistance to epidemiologically dominant GII.4 strains. Because future human vaccines will comprise and because secretor...
Mature DENVs represent the dominant form in vivo and are target for vaccine development. Here, we used multiple strategies, including protein engineering natural directed evolution to generate DENV1, -2, -3, -4 variants that highly mature without compromising replication efficiency compared parental strains.
The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 mRNA-1273 SARS-CoV-2 vaccines for infants 6 months older in June 2022. Yet questions regarding durability vaccine efficacy, especially against emerging variants, this age group remain. We demonstrated previously that a two-dose regimen stabilized prefusion Washington S-2P spike (S) protein encoded by mRNA encapsulated lipid nanoparticles (mRNA-LNP) or purified mixed with 3M-052, synthetic Toll-like...
Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, emergence SARS-CoV-2 variants concern (VOC) partially evade vaccine immunity remains a global health concern. In addition, highly mutated neutralization-resistant VOCs such as BA.1 BA.5 or fully (1) many therapeutic monoclonal antibodies in clinical use underlines need for additional treatment strategies. Here, we characterize antiviral activity GS-5245, Obeldesivir (ODV), an oral...
Noroviruses are the leading cause of acute gastroenteritis worldwide with GII.4 Sydney viruses responsible for majority infections until 2023. To study evolutionary dynamics noroviruses in US (2011-2023), we sequenced and analyzed 406 VP1 335 RdRp sequences submitted to CaliciNet. Time-scale analysis showed average rate strains was 5.56 x 10-3 substitutions/site/year emergence a new cluster within every 4 years starting Sydney[P31] from 2011-2015 followed by Sydney[P16] 2016-2020, most...
Abstract We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 noroviruses from United States, Gabon, South Africa, and Kingdom collected during 2017–2022. Early identification variants is crucial for assessing pandemic potential informing vaccine development.
Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for number of pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent major family contributing emerging in both human animal populations been recently identified bats. In this study, we blended metagenomics, phylogenetics, homology modeling, vitro assays characterize two novel bat calicivirus (BtCalV) capsid sequences,...