Safety, dose, immunogenicity, and transmissibility of an oral live attenuated Shigella flexneri 2a vaccine candidate (SC602) among healthy adults and school children in Matlab, Bangladesh

Rahman, Kazi Mizanur; Arifeen, Shams El; Zaman, Khalequz; Raqib, Rubhana; Yunus, Muhammad; Begum, Nazma; Islam, Md. Shaheenul; Sohel, Badrul Munir; Rahman, Mahbubur; Venkatesan, Malabi M.; Hale, Thomas L.; Isenbarger, Daniel W.; Sansonetti, Philippe J.; Black, Robert E.; Baqui, Abdullah H

doi:10.1016/j.vaccine.2010.10.035

Cited by 59 publications

(42 citation statements)

References 15 publications

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“…Several attempts have been made so far toward the development of a functional vaccine against shigellosis and several strategies for vaccine production have been exploited. Live-attenuated whole-cell oral vaccines were shown to induce a robust immune response, but as well a high risk of reactogenicity and reversion [17]. The approach of using inactivated whole-cell vaccines has been shown to be safe and immunogenic, when administered orally in volunteers at repeated high doses [18].…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study

Hatz

Bally

Rohrer³

et al. 2015

Vaccine

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Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study

Hatz

Bally

Rohrer³

et al. 2015

Vaccine

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“…The challenge with oral vaccines has been in finding the optimal balance between reactogenicity and immunogenicity. Furthermore, vaccines which appear immunogenic but somewhat reactogenic in volunteers from high-resource settings have been well-tolerated but overattenuated when given to adults and children in developing countries (33,34). Reviews of the pitfalls and successes of Shigella vaccine candidates under development have been published (8,(35)(36)(37).…”

mentioning

confidence: 99%

Shigella Vaccine Development: Finding the Path of Least Resistance

Chen

Kotloff

2016

Clin Vaccine Immunol

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-16) report results from a phase I study of a parenterally administered monovalent O-polysaccharide "bioconjugate" directed against Shigella flexneri 2a. Ultimately, the goal is to develop a broad-spectrum Shigella vaccine to address this public health concern. A parenteral Shigella vaccine capable of eliciting protection in children of developing countries would be an important tool to reach this goal.

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“…currently exists. Efforts to develop a vaccine against this pathogen have included the use of killed bacteria (31), live attenuated (1,19,22,38) and recombinant carrier (21) organisms, polysaccharide conjugates (7,36), and LPS-protein mixtures (16,48). When tested in humans, these vaccines were either too reactogenic or poorly immunogenic.…”

mentioning

confidence: 99%

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

et al. 2012

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Shigella spp. are food-and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the development of a broadly protective vaccine. All Shigella spp. utilize a type III secretion system (TTSS) to initiate infection. The type III secretion apparatus (TTSA) is the molecular needle and syringe that form the energized conduit between the bacterial cytoplasm and the host cell to transport effector proteins that manipulate cellular processes to benefit the pathogen. IpaB and IpaD form a tip complex atop the TTSA needle and are required for pathogenesis. Because they are common to all virulent Shigella spp., they are ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We examined the immunogenicity and protective efficacy of IpaB and IpaD, alone or combined, coadministered with a double mutant heat-labile toxin (dmLT) from Escherichia coli, used as a mucosal adjuvant, in a mouse model of intranasal immunization and pulmonary challenge. Robust systemic and mucosal antibody-and T cell-mediated immunities were induced against both proteins, particularly IpaB. Mice immunized in the presence of dmLT with IpaB alone or IpaB combined with IpaD were fully protected against lethal pulmonary infection with Shigella flexneri and Shigella sonnei. We provide the first demonstration that the Shigella TTSAs IpaB and IpaD are promising antigens for the development of a cross-protective Shigella vaccine.

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Safety, dose, immunogenicity, and transmissibility of an oral live attenuated Shigella flexneri 2a vaccine candidate (SC602) among healthy adults and school children in Matlab, Bangladesh

Cited by 59 publications

References 15 publications

Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study

Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study

Shigella Vaccine Development: Finding the Path of Least Resistance

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

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