Biomedical subjects

Susan C Stone

Publications and source records attributed to Susan C Stone.

6 recordsLinked to original sources

PubMed2006

Protection against rotavirus shedding after intranasal immunization of mice with a chimeric VP6 protein does not require intestinal IgA.

Intranasal immunization of mice with chimeric VP6 and the adjuvant LT(R192G) consistently elicits >95% reductions in fecal rotavirus shedding following challenge. To determine the association between mucosal antibody and protection, we immunized BALB/c wt and J chain knockout (Jch-/-) mice with VP6 and either LT(R192G) or cholera toxin (CT). Both strains developed nearly equal levels of serum rotavirus IgG, but Jch-/- mice, which cannot transport dimeric IgA across epithelial cell surfaces, developed >4-fold higher levels of serum rotavirus IgA. Stool rotavirus IgA was present in wt but undetectable in Jch-/- mice. When challenged with rotavirus strain EDIM, reductions in rotavirus shedding were nearly identical in VP6-immunized wt and Jch-/- mice (i.e., 97% and 92%, respectively; P > 0.01). Th1 CD4 T cell responses were also detected in VP6-immunized animals based on high levels of IFN-gamma and IL-2 found after in vitro VP6 stimulation of spleen cells. Therefore, protection induced by intranasal immunization of mice with VP6 and adjuvant does not depend on intestinal rotavirus IgA antibody but appears to be associated with CD4 T cells.

Adjuvants, Immunologic↗

PubMed2006

Mice develop effective but delayed protective immune responses when immunized as neonates either intranasally with nonliving VP6/LT(R192G) or orally with live rhesus rotavirus vaccine candidates.

Rotavirus vaccines are delivered early in life, when the immune system is immature. To determine the effects of immaturity on responses to candidate vaccines, neonatal (7 days old) and adult mice were immunized with single doses of either Escherichia coli-expressed rotavirus VP6 protein and the adjuvant LT(R192G) or live rhesus rotavirus (RRV), and protection against fecal rotavirus shedding following challenge with the murine rotavirus strain EDIM was determined. Neonatal mice immunized intranasally with VP6/LT(R192G) were unprotected at 10 days postimmunization (dpi) and had no detectable rotavirus B-cell (antibody) or CD4(+) CD8(+) T-cell (rotavirus-inducible, Th1 [gamma interferon and interleukin-2 {IL-2}]-, Th2 [IL-5 and IL-4]-, or ThIL-17 [IL-17]-producing spleen cells) responses. However, by 28 and 42 dpi, these mice were significantly (P >or= 0.003) protected and contained memory rotavirus-specific T cells but produced no rotavirus antibody. In contrast, adult mice were nearly fully protected by 10 dpi and contained both rotavirus immunoglobulin G and memory T cells. Neonates immunized orally with RRV were also less protected (P=0.01) than adult mice by 10 dpi and produced correspondingly less rotavirus antibody. Both groups contained few rotavirus-specific memory T cells. Protection levels by 28 dpi for neonates or adults were equal, as were rotavirus antibody levels. This report introduces a neonatal mouse model for active protection studies with rotavirus vaccines. It indicates that, with time, neonatal mice develop full protection after intranasal immunization with VP6/LT(R192G) or oral immunization with a live heterologous rotavirus and supports reports that protection depends on CD4(+) T cells or antibody, respectively.

Adjuvants, Immunologic↗

PubMed2005

Emphysematous pyelonephritis: clues to rapid diagnosis in the Emergency Department.

Emphysematous pyelonephritis (EPN) is an acute life-threatening bacterial infection. EPN leads to rapid necrotizing destruction of the renal parenchyma and peri-renal tissue, requiring early and aggressive care to reduce morbidity and mortality. Previous studies have described the use of computed tomography scan and radiology-performed ultrasound to make the diagnosis of EPN We report a case of EPN diagnosed by bedside Emergency Department (ED) ultrasound performed by emergency physicians, allowing a more rapid diagnosis and subsequent treatment.

Emergency Service, Hospital↗

PubMed2004

Pneumococcal vaccination in the emergency department: an assessment of need.

STUDY OBJECTIVES: Immunization against Streptococcus pneumoniae with the 23-valent pneumococcal polysaccharide vaccine has been shown to be cost-effective for prevention of invasive pneumococcal disease. Yet 23-valent pneumococcal polysaccharide vaccine is widely underused, particularly among ethnic minorities. The objectives of this survey are to determine the rate of 23-valent pneumococcal polysaccharide vaccine vaccination among all adult patients presenting to the emergency department (ED) of a county-based, urban, tertiary care medical center; the willingness of patients to receive 23-valent pneumococcal polysaccharide vaccine; and reasons for nonvaccination. METHODS: A quality assurance survey was performed in the ED during 3 days in September 2002. A survey was developed to determine 23-valent pneumococcal polysaccharide vaccine vaccination rates and eligibility according to indications and contraindications established by the Centers for Disease Control and Prevention (CDC). Descriptive statistics were performed to quantify the proportion of patients who were immunized, eligible, and willing to receive 23-valent pneumococcal polysaccharide vaccine and reasons for nonvaccination. RESULTS: A total of 250 patients of 1,535 registered in the ED were surveyed during the 3-day period. Only 48 (19%) had a primary care provider. The majority of patients were Hispanic (73%). Only 22 (9%) patients had received the vaccine. A total of 66 (26%) patients fit the CDC eligibility criteria for 23-valent pneumococcal polysaccharide vaccine, and 59 (89%) of these patients were willing to receive the vaccine during their ED visit. Most patients (79%) were eligible to receive 23-valent pneumococcal polysaccharide vaccine due to their comorbid illnesses. CONCLUSION: In the ED of our county-based urban medical center, 26% of patients were eligible for 23-valent pneumococcal polysaccharide vaccine; the majority of patients were Hispanic, unaware of the vaccine's existence, and willing to receive it during their ED visit. These data underscore a large unmet public health need among ethnic minorities in the ED.

Adult↗

PubMed2002

Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses.

Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6 protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2(d)) mice along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat-labile toxin, has been found to consistently stimulate ca. 99% reductions in rotavirus shedding after subsequent EDIM challenge. This study was designed to determine the robustness of this protection, i.e. can VP6 immunization consistently protect against shedding in this model, thus, providing an indication of its potential as a vaccine. Intranasal immunization with two 8.8 microg doses of EDIM VP6 and 10 microg of LT(R192G) was found to stimulate 99% reductions in EDIM shedding in four additional strains of inbred mice belonging to three haplotypes, i.e. DBA/2 (H-2(d)), C57BL/6 (H-2(b)), 129 (H-2(b)) and C3H (H-2(k)). Protection stimulated against EDIM antigen shedding following i.n. immunization with VP6 from the human CJN strain was less (P=0.02) than induced by EDIM VP6 (86% versus 99%), but no further loss of protection was observed when the dose of CJN VP6 was reduced 100-fold. Protection against EDIM shedding was also maintained after i.n. immunization of three strains of outbred mice (CF-1, CD-1 and Swiss Webster) with either EDIM or CJN VP6, i.e. EDIM VP6 immunization reduced EDIM shedding by 99% while CJN VP6 immunization produced reductions of 86-96%. Protection stimulated by oral immunization of BALB/c mice with two 8.8 microg doses of either VP6 chimera plus LT(R192G) was not significantly different from that induced by i.n. immunization. Finally, protection found after either oral or i.n. immunization with EDIM or CJN VP6 was no different when the mice were challenged with McN, another strain of murine rotavirus. These results support further evaluation of VP6 as a vaccine.

Administration, Intranasal↗

PubMed2002

CD4 T cells are the only lymphocytes needed to protect mice against rotavirus shedding after intranasal immunization with a chimeric VP6 protein and the adjuvant LT(R192G).

Intranasal immunization of mice with a chimeric VP6 protein and the mucosal adjuvant Escherichia coli heat labile toxin LT(R192G) induces nearly complete protection against murine rotavirus (strain EDIM [epizootic diarrhea of infant mice virus]) shedding for at least 1 year. The aim of this study was to identify the protective lymphocytes elicited by this new vaccine candidate. Immunization of mouse strains lacking one or more lymphocyte populations revealed that protection was dependent on alphabeta T cells but mice lacking gammadelta T cells and B cells remained fully protected. Furthermore, depletion of CD8 T cells in immunized B-cell-deficient mice before challenge resulted in no loss of protection, while depletion of CD4 T cells caused complete loss of protection. Therefore, alphabeta CD4 T cells appeared to be the only lymphocytes required for protection. As confirmation, purified splenic T cells from immunized mice were intraperitoneally injected into Rag-2 mice chronically infected with EDIM. Transfer of 2 x 10(6) CD8 T cells had no effect on shedding, while transfer of 2 x 10(5) CD4 T cells fully resolved shedding in 7 days. Interestingly, transfer of naive splenic CD4 T cells also resolved shedding but more time and cells were required. Together, these results establish CD4 T cells as effectors of protection against rotavirus after intranasal immunization of mice with VP6 and LT(R192G).

Adjuvants, Immunologic↗