A5046510431- Immunotherapy and Immune Responses
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Mosquito-borne diseases and control
- Immune Response and Inflammation
- Viral Infections and Vectors
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Animal Disease Management and Epidemiology
- HIV-related health complications and treatments
- Animal Virus Infections Studies
- HIV/AIDS Research and Interventions
- Vector-Borne Animal Diseases
- Immune responses and vaccinations
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Malaria Research and Control
- Complement system in diseases
- Reproductive System and Pregnancy
University of Pittsburgh
2014-2025
Institut de Recherche Vaccinale
2007-2014
Faculty of Public Health
2000-2008
University of California, Davis
1993-1995
Veterinary Medical Teaching Hospital
1993
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with disease 2019 (COVID-19), but it not clear whether this RNAemia reflects viremia (ie, virus particles) and how relates to host immune responses outcomes. Methods SARS-CoV-2 vRNA was quantified plasma samples from observational cohorts 51 COVID-19 including 9 outpatients, 19 hospitalized (non–intensive care unit [ICU]), 23 ICU patients. levels...
Abstract Dendritic cells (DC) can readily capture Ag from dead and dying for presentation to MHC class I-restricted CTL. We now show by using a primate model that DC also acquire healthy cells, including other DC. Coculture assays showed fluorescently labeled plasma membrane was rapidly efficiently transferred between DC, transfer of intracellular proteins observed lesser extent. Acquisition protein cell contact-dependent primarily function immature whereas both CD40L-matured could serve as...
ABSTRACT The recent emergence of highly pathogenic avian influenza virus (HPAI) strains in poultry and their subsequent transmission to humans Southeast Asia have raised concerns about the potential pandemic spread lethal disease. In this paper we describe development testing an adenovirus-based A vaccine directed against hemagglutinin (HA) protein A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during human outbreak Vietnam from 2003 2005. We expressed different portions HA a...
Monocyte-derived dendritic cells (DC) possess the unique capacity to capture Ag from live through intimate cell contact, a process referred as nibbling. We sought define receptor(s) mediating DC Uptake of fluorescently labeled plasma membrane by was inhibited protease treatment and panel polyanionic ligands, implicating scavenger receptors (SR) in this process. Differential expression SR on macrophages correlated with acquire cells. Internalized colocalized ligand entered endosomal pathway....
Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants concern have independently been shown to enhance aspects protein fitness. Here, we describe an antibody fragment (V H ab6) that neutralizes all major including recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode binding revealed by cryo-EM studies. Further, provide comparative analysis mutational effects within previously variant spikes identify structural role mutations NTD RBD evading neutralization....
Severe influenza kills tens of thousands individuals each year, yet the mechanisms driving lethality in humans are poorly understood. Here we used a unique translational model lethal H5N1 cynomolgus macaques that utilizes inhalation small-particle virus aerosols to define disease. RNA sequencing lung tissue revealed an intense interferon response within two days infection resulted widespread expression interferon-stimulated genes, including inflammatory cytokines and chemokines. Macaques...
The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model acute SARS-CoV-2 infection to delineate perturbations in innate immune system. initiates rapid infiltration plasmacytoid dendritic cells into lower airway, commensurate with IFNA production, natural killer cell activation, and significant increase blood CD14
Influenza virus pandemics and seasonal epidemics have claimed countless lives. Recurrent zoonotic spillovers of influenza viruses with pandemic potential underscore the need for effective countermeasures. In this study, we show that pre-exposure prophylaxis broadly neutralizing antibody (bnAb) MEDI8852 is highly in protecting cynomolgus macaques from severe disease caused by aerosolized pathogenic avian H5N1 infection. Protection was dose–dependent yet independent Fc-mediated effector...
Abstract Human dendritic cells (DC) have polarized responses to chemokines as a function of maturation state, but the effect on DC trafficking in vivo is not known. We addressed this question highly relevant rhesus macaque model. demonstrate that immature and CD40 ligand-matured monocyte-derived characteristic phenotypic functional differences vitro. In particular, express CC chemokine receptor 5 (CCR5) migrate response macrophage inflammatory protein-1α (MIP-1α), whereas mature switch...
Plasmacytoid dendritic cells (pDC) are essential innate immune system that lost from the circulation in human immunodeficiency virus (HIV)-infected individuals associated with CD4(+) T cell decline and disease progression. pDC depletion is thought to be caused by migration tissues or death, although few studies have addressed this directly. We used precise methods of enumeration vivo labeling 5-bromo-2'-deoxyuridine track recently divided blood tissue compartments monkeys acute pathogenic...
Abstract The loss of myeloid (mDC) and plasmacytoid dendritic cells (pDC) from the blood HIV-infected individuals is associated with progressive disease. It has been proposed that DC due to increased recruitment lymph nodes, although this not directly tested. Similarly as in humans, we found lineage-negative (Lin−) HLA-DR+CD11c+CD123− mDC Lin−HLA-DR+CD11c−CD123+ pDC were lost SIV-infected rhesus macaques AIDS. In peripheral nodes SIV-naive monkeys majority mature derived skin expressed high...
Dengue is a globally expanding disease caused by infection with dengue virus (DENV) that ranges from febrile illness to acute serious complications. Secondary predisposes individuals more severe disease, and B lymphocytes may play role in this phenomenon through production of Ab enhance infection. To better define the cell response during dengue, we analyzed peripheral cells an adult Brazilian hospital cohort primary secondary DENV infections varying clinical severity. Circulating patients...
Dendritic cells with potent Ag-presenting function can be propagated from peripheral blood using recombinant cytokines, and these have potential usefulness as immunotherapeutic agents in the treatment of cancer other disease states. However, it is not known if vitro differentiated dendritic capacity to migrate vivo, especially T cell areas lymphoid tissue. We used a fluorescent marker system track migration cells, chimpanzee blood, following s.c. injection. report that injected spontaneously...
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated intense production proinflammatory cytokines, whether this cytokine storm main cause fatality or a consequence extensive replication that itself drives remains controversial. Conventional intratracheal inoculation liquid suspension in nonhuman primates likely results efficient clearance within upper respiratory tract and...
Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this lacking. We used dual antagonist Toll-like receptor (TLR) 7 and TLR9 selectively inhibit responses pDC not other mononuclear phagocytes viral RNA prior 8 weeks following pathogenic simian (SIV) rhesus macaques. show that are major exclusive producers IFN-α rapidly...
Myeloid dendritic cells (mDC) are lost from blood in individuals with human immunodeficiency virus (HIV) infection but the mechanism for this loss and its relationship to disease progression not known. We studied mDC response lymph nodes of simian (SIV)-infected rhesus macaques different outcomes. Early changes number were inversely correlated load reflective eventual outcome, as animals stable that remained disease-free more than one year had average increases 200% over preinfection levels...