PubMed Health⌕ Search

Biomedical subjects

Eric Donaldson

Publications and source records attributed to Eric Donaldson.

4 recordsLinked to original sources
PubMed2006

Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.

BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge. METHODS AND FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV-challenged mice. VRP-N-induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.

Aging↗
PubMed2002

Potential multiple endonuclease functions and a ribonuclease H encoded in retroposon genomes.

Among the retroposons, the source of the endonuclease activity is known to be variable and can be provided as either a retroviral-like integrase or a protein similar to the cellular apurinic-apyrimidinic endonuclease. It has also been reported that other retroposon and retrointron sequences have limited similarity to various eubacterial endonucleases. We investigated whether any retroposon genomes possibly encode multiple endonuclease functions. Amino acid alignments were generated and analyzed for the presence of the characterized ordered-series-of-motifs (OSM) representative of four different endonuclease functions. The results indicate that SLACS, CZAR, CRE1, CRE2, and some Trypanosoma brucei retroposon sequences encode multiple putative endonuclease functions. Interestingly, one of the endonuclease functions is embedded within the potential ribonuclease H sequence found in SLACS, CZAR, CRE1, CRE2, and R2BM retroposons.

Amino Acid Sequence↗