A modified Shigella volunteer challenge model in which the inoculum is administered with bicarbonate buffer: clinical experience and implications for Shigella infectivity

Kotloff, Karen L.; Nataro, James P.; Losonsky, Genevieve A.; Wasserman, Steven S.; Hale, Thomas L.; Taylor, David N.; Sadoff, Jerald C.; Levine, Myron M.

doi:10.1016/0264-410x(95)00102-7

Cited by 106 publications

(119 citation statements)

References 21 publications

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“…Vaccine-induced protective immunity that was serotype specific was demonstrated in field trials evaluating both streptomycin-dependent oral vaccines (18) and a parenteral S. sonnei O-antigen-specific polysaccharide conjugate vaccine (3). Similarly, homotypic immunity conferred by wild-type infection has been found in animal models (6), in epidemiologic studies (5), and in volunteer challenge experiments (8,11). A response that has been correlated with protective efficacy in clinical trials is the anti-Shigella LPS IgA ASC count, which presumably reflects the degree of mucosal priming induced by an immunogen (10).…”

Section: Discussionmentioning

confidence: 97%

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Phase I Evaluation of Δ virG Shigella sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults

et al. 2002

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We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral ⌬virG Shigella sonnei vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (n ‫؍‬ 7) or vaccine (n ‫؍‬ 27) at 3 ؋ 10 3 CFU (group 1), 3 ؋ 10 4 CFU (group 2), 3 ؋ 10 5 CFU (group 3), or 3 ؋ 10 6 CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients. WRSS1 was recovered from the stools of 50 to 100% of the vaccinees in each group. The geometric mean peak anti-lipopolysaccharide responses in groups 1 to 4, respectively, were 99, 39, 278, and 233 for immunoglobulin (IgA) antibody-secreting cell counts; 401, 201, 533, and 284 for serum reciprocal IgG titers; and 25, 3, 489, and 1,092 for fecal IgA reciprocal titers. Postvaccination increases in gamma interferon production in response to Shigella antigens occurred in some volunteers. We conclude that WRSS1 vaccine is remarkably immunogenic in doses ranging from 10 3 to 10 6

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Section: Discussionmentioning

confidence: 97%

“…Vaccine excretion was detected by culturing all of the stools passed during inpatient isolation and once weekly for 3 weeks after discharge by using previously published methods (11). Excretion was quantified for 6 days after vaccination as previously described (11).…”

Section: Methodsmentioning

confidence: 99%

Phase I Evaluation of Δ virG Shigella sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults

et al. 2002

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“…Protocols were approved by the institutional review board of the University of Maryland (BB-IND 6521). In a stepwise fashion, groups of volunteers were challenged orally with SC595 in a bicarbonate solution as described in earlier trials involving S. flexneri 2a (20). The inoculum contained 3 ϫ 10 2 , 7 ϫ 10 3 , 5 ϫ 10 4 , or 7 ϫ 10 5 CFU of SC595.…”

Section: Subjects and Clinical Protocolsmentioning

confidence: 99%

Production of IFN-γ and IL-10 to Shigella Invasins by Mononuclear Cells from Volunteers Orally Inoculated with a Shiga Toxin-Deleted Shigella dysenteriae Type 1 Strain

Samandari

Kotloff

Losonsky

et al. 2000

The Journal of Immunology

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Volunteers were orally administered invasive, non-Shiga toxin-producing Shigella dysenteriae 1 to establish a challenge model to assess vaccine efficacy. In stepwise fashion, four separate groups were given 3 × 102, 7 × 103, 5 × 104, or 7 × 105 CFU. Using PBMC, proliferative responses and cytokine production were measured to S. dysenteriae whole-cell preparations and to purified recombinant invasion plasmid Ags (Ipa) C and IpaD. Anti-LPS and anti-Ipa Abs and Ab-secreting cells were also evaluated. Preinoculation PBMC produced considerable quantities of IL-10 and IFN-γ, probably secreted by monocytes and NK cells, respectively, of the innate immune system. Following inoculation, PBMC from 95 and 87% of volunteers exhibited an increased production of IFN-γ and IL-10, respectively, in response to Shigella Ags. These increases included responses to IpaC and IpaD among those volunteers receiving the lowest inoculum. No IL-4 or IL-5 responses were detected. Whereas there were no Ab or Ab-secreting cell responses in volunteers receiving the lowest inoculum, other dose groups had moderate to strong anti-LPS and anti-Ipa responses. These results suggest that in humans, type 1 responses play an important role in mucosal and systemic immunity to S. dysentariae 1.

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“…Quantitative culture methods demonstrated that volunteers with diarrhea tend to have higher quantities of bacteria isolated from their stool than do those without diarrhea (6,7,8). Similarly, other studies have used qPCR to investigate the causes of the intestinal disease associated with norovirus and Escherichia coli (9,10).…”

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Quantitative PCR for Detection of Shigella Improves Ascertainment of Shigella Burden in Children with Moderate-to-Severe Diarrhea in Low-Income Countries

et al. 2013

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Estimates of the prevalence of Shigella spp. are limited by the suboptimal sensitivity of current diagnostic and surveillance methods. We used a quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533 children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or without moderate-to-severe diarrhea (MSD). We compared the results from conventional culture to those from qPCR for the Shigella ipaH gene. Using MSD as the reference standard, we determined the optimal cutpoint to be 2.9 ؋ 10 4 ipaH copies per 100 ng of stool DNA for set 1 (n ‫؍‬ 877). One hundred fifty-eight (18%) specimens yielded >2.9 ؋ 10 4 ipaH copies. Ninety (10%) specimens were positive by traditional culture for Shigella. Individuals with >2.9 ؋ 10 4 ipaH copies have 5.6-times-higher odds of having diarrhea than those with <2.9 ؋ 10 4 ipaH copies (95% confidence interval, 3.7 to 8.5; P < 0.0001). Nearly identical results were found using an independent set of samples. qPCR detected 155 additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172 cases detected by culture in both samples. Among a subset (n ‫؍‬ 2,874) comprising MSD cases and their age-, gender-, and location-matched controls, the fraction of MSD cases that were attributable to Shigella infection increased from 9.6% (n ‫؍‬ 129) for culture to 17.6% (n ‫؍‬ 262) for qPCR when employing our cutpoint. We suggest that qPCR with a cutpoint of approximately 1.4 ؋ 10 4 ipaH copies be the new reference standard for the detection and diagnosis of shigellosis in children in low-income countries. The acceptance of this new standard would substantially increase the fraction of MSD cases that are attributable to Shigella.

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A modified Shigella volunteer challenge model in which the inoculum is administered with bicarbonate buffer: clinical experience and implications for Shigella infectivity

Cited by 106 publications

References 21 publications

Phase I Evaluation of Δ virG Shigella sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults

Phase I Evaluation of Δ virG Shigella sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults

Production of IFN-γ and IL-10 to Shigella Invasins by Mononuclear Cells from Volunteers Orally Inoculated with a Shiga Toxin-Deleted Shigella dysenteriae Type 1 Strain

Quantitative PCR for Detection of Shigella Improves Ascertainment of Shigella Burden in Children with Moderate-to-Severe Diarrhea in Low-Income Countries

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