ORCID Profile
0000-0003-3603-1733
Current Organisations
University of California, San Diego
,
Veterans Affairs Mecical Center
,
Veterans Affairs Medical Center
,
San Diego Center For Aids Research
,
Family Health Centers of San Diego
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Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2020
DOI: 10.1101/2020.12.08.416750
Abstract: T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens, and precisely measure virus-specific CD4 + and CD8 + T cells, we studied epitope-specific T cell responses of approximately 100 convalescent COVID-19 cases. The SARS-CoV-2 proteome was probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of HLA alleles for class II responses. For HLA class I, we studied an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identified several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance were observed, which differed for CD4 + T cells, CD8 + T cells, and antibodies. The class I and class II epitopes were combined into new epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4 + and CD8 + T cells.
Publisher: Public Library of Science (PLoS)
Date: 07-04-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-10-2020
Abstract: Robust T cell responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus occur in most in iduals with coronavirus disease 2019 (COVID-19). Several studies have reported that some people who have not been exposed to SARS-CoV-2 have preexisting reactivity to SARS-CoV-2 sequences. The immunological mechanisms underlying this preexisting reactivity are not clear, but previous exposure to widely circulating common cold coronaviruses might be involved. Mateus et al. found that the preexisting reactivity against SARS-CoV-2 comes from memory T cells and that cross-reactive T cells can specifically recognize a SARS-CoV-2 epitope as well as the homologous epitope from a common cold coronavirus. These findings underline the importance of determining the impacts of preexisting immune memory in COVID-19 disease severity. Science , this issue p. 89
Publisher: American Medical Association (AMA)
Date: 12-07-2016
Publisher: American Society for Microbiology
Date: 10-2017
DOI: 10.1128/AAC.00954-17
Abstract: Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii . We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-02-2021
Abstract: Immune memory against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helps to determine protection against reinfection, disease risk, and vaccine efficacy. Using 188 human cases across the range of severity of COVID-19, Dan et al. analyzed cross-sectional data describing the dynamics of SARS-CoV-2 memory B cells, CD8 + T cells, and CD4 + T cells for more than 6 months after infection. The authors found a high degree of heterogeneity in the magnitude of adaptive immune responses that persisted into the immune memory phase to the virus. However, immune memory in three immunological compartments remained measurable in greater than 90% of subjects for more than 5 months after infection. Despite the heterogeneity of immune responses, these results show that durable immunity against secondary COVID-19 disease is a possibility for most in iduals. Science , this issue p. eabf4063
Publisher: Research Square Platform LLC
Date: 18-04-2023
DOI: 10.21203/RS.3.RS-2694520/V1
Abstract: The prevalence of “Long COVID”, including among vaccinated patients, is just one of the conundrums that indicate how much remains unknown about the lung’s response to viral infection, particularly to SARS-CoV-2 for which the lung is the point of entry. Therefore, we used an in vitro human lung system to enable a prospective, unbiased, sequential single cell level analysis of pulmonary cell responses following infection by multiple strains of SARS-CoV-2. By starting with human induced pluripotent stem cells (hiPSCs) and emulating lung organogenesis, three-dimensional lung organoids were generated and infected in which several unexpected but pertinent insights emerged. First, SARS-CoV-2 tropism is much broader than previously believed: most lung cell types can be infected, if not through a canonical receptor-mediated route (e.g., via ACE2) then via a non-canonical “backdoor” endocytosis/micropinocytosis route. Such entry can be abrogated by FDA-approved endocytosis blockers, suggesting novel adjunctive therapies. Regardless of route-of-entry, the virus triggers a heretofore unrecognized lung epithelial cell-intrinsic autonomous innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic cells or their derivatives. The virus can spread rapidly throughout human lung organoid cell cultures resulting in mitochondrial apoptosis mediated by the pro-survival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in part, dependent on the presence of pulmonary Surfactant Protein-B (SP-B), which plays an unanticipated role in signal transduction, viral resistance, d ens systemic inflammatory cytokine production, and minimizes the induction of apoptosis.
Location: United States of America
Location: United States of America
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Davey Smith.