A5003959361- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- T-cell and B-cell Immunology
- Respiratory viral infections research
- Viral Infectious Diseases and Gene Expression in Insects
- HIV Research and Treatment
- RNA Interference and Gene Delivery
- Influenza Virus Research Studies
- Viral Infections and Immunology Research
- SARS-CoV-2 detection and testing
- interferon and immune responses
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Long-Term Effects of COVID-19
- RNA Research and Splicing
- Cytomegalovirus and herpesvirus research
- Biomedical and Engineering Education
- CRISPR and Genetic Engineering
- Innovations in Medical Education
- Viral Infections and Vectors
- Herpesvirus Infections and Treatments
Institute of Immunology
2022
University of Minnesota
2020-2021
Minot State University
2021
University of Minnesota Medical Center
2020-2021
Mayo Clinic
2015-2020
Mayo Clinic in Arizona
2015-2018
Mayo Clinic in Florida
2017-2018
WinnMed
2015
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with human adenovirus type 5 vector expressing SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian...
The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how heterogeneity this diverse population contributes elements viral tropism pathogenesis, antiviral immunity, treatment response remdesivir. found that, while a variety epithelial types are susceptible infection, ciliated cells predominant target SARS-CoV-2. host protease TMPRSS2 was required for infection these cells. Importantly, remdesivir...
ABSTRACT Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections negative-strand RNA viruses and outgrow full-length genomes, thereby modulating severity duration infection. Here we document frequent de novo generation copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) wild-type (IC323) as early passage 1 after rescue. Moreover, C-protein-deficient (C-protein-knockout [C KO ]) generated about 10 times more than parental virus,...
Abstract The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited may bolster durable protection or cross-reactivity variants. To better enable mechanistic and vaccination studies mice, we identified a dominant CD8 SARS-CoV-2 nucleoprotein epitope. Infection ACE2 transgenic mice elicited robust...
ABSTRACT Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based demonstrated that these viral vectors can mediate more potent protection against virus infection in animal models. In most cases, Ad are engineered to be replication-defective (RD-Ad) vectors. contrast, replication-competent (RC-Ad) markedly but risk causing diseases vaccine recipients and health care workers. To harness antigen gene replication avoid production infectious virions, we...
Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet be exploited for development SARS-CoV-2 therapeutics. Here, we detail identification a series VNAR phage display library screened against receptor domain (RBD). The ability neutralize pseudotype and authentic live virus...
Abstract Background The transfer of passive immunity with convalescent plasma is a promising strategy for treatment and prevention COVID‐19, but donors history nonsevere disease are serologically heterogenous. relationship between SARS‐Cov‐2 antigen–binding activity neutralization in this population has not been defined. Study Design Methods Convalescent units from 47 individuals COVID‐19 were assessed antigen‐binding using three clinical diagnostic serology assays (Beckman, DiaSorin, Roche)...
For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not antigen-specific recognition a priori knowledge of the causative agent. However, it is unclear whether effective stable activation can be achieved without triggering harmful autoimmunity other chronic inflammatory sequelae. Here, we show transgenic...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with HAd5 expressing nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters k18-hACE2...
Recent West African Ebola virus (EBOV) epidemics have led to testing different anti-EBOV vaccines, including a replication-defective adenovirus (RD-Ad) vector (ChAd3-EBOV) and an infectious, replication-competent recombinant vesicular stomatitis expressing the EBOV glycoprotein (rVSV-EBOV; also known as rVSV-ZEBOV). While RD-Ads elicit protection, when scaled up human trials, level of protection may be much lower than that vaccines containing viruses can replicate. Although Ad (RC-Ad)...
Most human immunodeficiency virus type 1 (HIV-1) infections begin at mucosal surfaces. Providing a barrier of protection these may assist in combating the earliest events infection. Systemic immunization by intramuscular (i.m.) injection can drive immune responses, but there are data suggesting that better educate responses. To test this, rhesus macaques were immunized with replicating single-cycle adenovirus (SC-Ad) vaccines expressing clade B HIV-1 gp160 intranasal (i.n.) and i.m. routes...
Most infections occur at mucosal surfaces. Providing a barrier of protection these surfaces may be useful strategy to combat the earliest events in infection when there are relatively few pathogens address. The majority vaccines delivered systemically by intramuscular (IM) route. While IM vaccination can drive immune responses, immunization intranasal (IN) or oral sites lead better responses viral entry. In macaques, IN with replicating single-cycle adenovirus (SC-Ads) and protein boosts...
HIV-1 infections occur during sexual contact at mucosal surfaces.Vaccines need to provide barrier protection and stimulate systemic immune responses control HIV spread.Most vaccines are delivered by immunization via intramuscular (IM) injection route.While this can drive responses, there data show that may be superior driving barriers.To explore question, we immunized mice with replicating single-cycle adenovirus (SC Ad) expressing clade B envelope (Env) (IM), intranasal (IN), or...
Clostridium difficile causes nearly 500,000 infections and 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. C. infection (CDI) arises from bacteria colonizing large intestine releasing two toxins, toxin A (TcdA) B (TcdB). Generating humoral immunity against difficile’s toxins provides protection primary recurrence. Thus, a vaccine may offer best opportunity for sustained, long-term protection. We developed novel single-cycle adenovirus (SC-Ad) expressing...
Immunosuppressed patients with inflammatory bowel disease (IBD) generate lower amounts of SARS-CoV-2 spike antibodies after mRNA vaccination than healthy controls. We assessed S1 receptor binding domain–specific (S1-RBD–specific) B lymphocytes to identify the underlying cellular defects. Patients IBD produced fewer anti–S1-RBD antibody–secreting cells controls first and total neutralizing second. S1-RBD–specific memory were generated same degree in control groups numerically stable for 5...
Abstract We determined the antigen binding activity of convalescent plasma units from 47 individuals with a history non-severe COVID-19 using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) different SARS-CoV-2 targets. compared these results functional neutralization fluorescent reporter strain in microwell assay. This revealed positive correlations varying strength (Spearman r = 0.37-0.52) between neutralization. Donors age 48-75 had highest activity. Units tertile...
Abstract The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how heterogeneity this diverse population contributes elements viral tropism pathogenesis, antiviral immunity, treatment response remdesivir. found that, while a variety epithelial types are susceptible infection, ciliated cells predominant target SARS-CoV-2. host protease TMPRSS2 was required for infection these cells. Importantly, remdesivir...
Abstract Coronavirus disease 2019 (COVID-19) outcomes are linked to host immune responses and may be affected by antiviral therapy. We investigated antibody cytokine in ACTT-1 study participants enrolled at our center. studied serum specimens from 19 hospitalized adults with COVID-19 randomized treatment remdesivir or placebo. assessed severe acute respiratory syndrome coronavirus 2 identified signatures, using hierarchical clustering. no clear immunologic trends attributable treatment....
Abstract Most adenovirus vaccines are replication-defective RD-Ads. In contrast, replication-competent (RC-Ad) replicate antigen genes 10,000-fold in each cell to amplify immune responses. While RC-Ads more potent than RD-Ad, they risk causing infections humans. We engineered “single-cycle” Ad (SC-Ad) vectors that still transgenes, but do not produce infectious progeny. RD-, SC-, and were tested by single immunization against influenza, Ebola virus, HIV-1, Zika HCV, CMV, Clostridium...
Mayo Clinic annually trains over 1000 predoctoral students and postdoctoral research fellows in medicine biomedical sciences. However, training opportunities are limited for those interested teaching mentoring methodologies. Therefore, sought to provide trainee‐led learning fellow trainees. A survey was sent all trainees determine preferences pedagogy education formats. In response results, the Twin Talk Series developed. is a set of one‐hour talks comprised Take‐in session one or more...