A5063024384- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- SARS-CoV-2 detection and testing
- Viral Infections and Immunology Research
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Outbreaks Research
- Blood groups and transfusion
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Insect symbiosis and bacterial influences
- COVID-19 Impact on Reproduction
- Immunotherapy and Immune Responses
- Malaria Research and Control
- Virus-based gene therapy research
- Respiratory viral infections research
- Dengue and Mosquito Control Research
- Protein purification and stability
- CAR-T cell therapy research
- Gas Sensing Nanomaterials and Sensors
- Galectins and Cancer Biology
- vaccines and immunoinformatics approaches
- Advanced Chemical Sensor Technologies
University of North Carolina at Chapel Hill
2020-2025
Public Health Department
2022-2023
<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...
We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding (RBD) antibodies. This imprint persists after secondary exposures wherein >60% ensuing...
Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against serotype 2 (DENV2), we evaluated the role of genetic diversity within pre-membrane (prM) and envelope (E) proteins DENV2 on vaccine performance. We generated a recombinant genotype variant panel with contemporary prM E isolates that are representative global diversity. The variants differ in growth kinetics, morphology, virion stability. Importantly,...
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 A potential outbreak of swine acute diarrhea syndrome coronavirus (SADS-CoV) in the human population could be devastating. Using genomewide CRISPR knockout screening, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection, uncovering a novel antiviral target CoV infection. The PLAC8-related pathway may also have implications other infections. Given ability to infect primary cultures without adaptation, our findings lay foundation...
Abstract The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others implicated in enhanced viral replication more severe Current tetravalent vaccines contain live attenuated formulated to theoretically induce balanced protective immunity. Among the number of candidates clinical trials, only Dengvaxia licensed for use DENV seropositive individuals. To...
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...
We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary post-vaccination, mainly an anti-spike antibody response S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% ensuing serological originating from initial...
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) has seen multiple anti-SARS-CoV-2 antibodies being generated globally. It is difficult, however, to assemble a useful compendium of these biological properties if they are derived from experimental measurements performed at different sites under conditions. Coronavirus Immunotherapeutic Consortium (COVIC) circumvents issues experimentally testing blinded side for several functional...
Abstract The rapid spread of the highly mutated SARS-CoV-2 Omicron variant has raised substantial concerns about protective efficacy currently available vaccines. We assessed Omicron-specific humoral and cellular immune responses in 65 individuals who were vaccinated with two immunizations BNT162b2 boosted after at least 6 months either Ad26.COV2.S (Johnson & Johnson; N=41) or (Pfizer; N=24) (Table S1).
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated temporally across the pandemic starting with first emergence virus in western hemisphere evaluated immune escape among variants. A clinic-to-lab viral isolation characterization pipeline was established rapidly isolate, sequence, characterize neutralization assay applied quantitate humoral immunity from infection and/or vaccination. panel novel monoclonal antibodies for antiviral efficacy. directly compared all...
The recommended COVID-19 booster vaccine uptake is low. At-home lateral flow assay (LFA) antigen tests are widely accepted for detecting infection during the pandemic. Here, we present feasibility and potential benefits of using LFA-based antibody as a means individuals to detect inadequate immunity make informed decisions about immunization. In health care provider cohort, investigated changes in breadth depth humoral T cell immune responses following mRNA vaccination boosting LFA-positive...
The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development therapeutic countermeasures provide broad protection against and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine recognize conserved epitopes in receptor binding domain (RBD) femtomolar affinities. Longitudinal analysis revealed progressive...
The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target SARS-CoV-2 NTD potently neutralize virus. This finding suggests may contribute, part, to protective immunity. Pansarbecovirus are desirable for broad protection, but region SARS-CoV and exhibit a high level sequence divergence; therefore, cross-reactive NTD-specific unexpected, there no structure antibody complex with NTD. Here, we report...
ABSTRACT The DENV envelope (E) and pre-membrane (prM) glycoproteins are primary targets of serologic immunity after infection vaccination. Of these, serotype-specific (TS) antibodies typically target E domains, while serotype cross-reactive (CR) the prM protein conserved regions. To identify quantify E-domain TS neutralizing antibody responses in polyclonal sera, we developed a panel chimeric DENV4/2 viruses that incorporate DENV2 domain I, II, III (DENV4/2-EDI, EDII, EDIII) into DENV4...
Individuals with weaker neutralizing responses show reduced protection SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated dynamics changes in breadth depth blood salivary antibodies as...
To evaluate SARS-CoV-2 variants we isolated temporally during the pandemic starting with first appearance of virus in Western hemisphere near Seattle, WA, USA, and each known major variant class, revealing dynamics emergence complete take-over all new cases by current Omicron variants. We assessed neutralization a first-ever full comparison across evaluated novel monoclonal antibody (Mab). found that convalescence greater than 5-months provides little-to-no protection against variants,...
Abstract Early life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate infant vaccination, we immunized two groups of 8 rhesus macaques (RMs) at weeks 0 4 with stabilized prefusion S-2P spike (S) protein, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed 3M-052-SE, a TLR7/8 agonist squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG neutralizing...