Parenteral immunization with IpaB/IpaD protects mice against lethal pulmonary infection by Shigella

Martinez-Becerra, Francisco J.; Scobey, Micah S.; Harrison, Kelly S.; Choudhari, Shyamal P.; Quick, Amy M; Joshi, Sangeeta B.; Middaugh, C. Russell; Picking, Wendy L.

doi:10.1016/j.vaccine.2013.04.012

Cited by 39 publications

(38 citation statements)

References 33 publications

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“…54 It has been reported that both humoral and T-cell immune responses were induced when Shigella IpaB/IpaD was co-administered with double mutant heat labile toxin and that this protected the mice from Shigella challenge. 20,[55][56][57] Furthermore, we observed that the rIpaB domain region alone conferred 60%-70% protection against Shigella spp. Interestingly, when rGroEL was administered along with the rIpaB domain, the survival percentage of the mice increased to 80%-85% protection against the lethal infection by Shigella spp., indicating an adjuvant effect of rGroEL.…”

Section: Discussionmentioning

confidence: 73%

“…[15][16][17][18][19][20] Recently, the crystal structure of a proteasestable fragment that was identified within the N-terminal region of IpaB from S. flexneri was presented; this fragment has substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens. 15 Early studies predicted that the domain regions of IpaB were necessary for invasion, phagosome escape, caspase-1 binding and cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

et al. 2015

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Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-c) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

et al. 2015

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“…Splenocytes (obtained at day 56) were incubated with 10 g/ml of IpaB, IpaD, or PBS for 48 h at 37°C. Secreted interleukin 17 (IL-17) levels were measured using the DuoSet ELISA development kit (22) or using a Th1/Th2 multiplex cytokine plate (Meso Scale Discovery, Gaithersburg, MD).…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

et al. 2013

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Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly ␣-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against Shigella flexneri and S. sonnei in the lethal pulmonary challenge. It also offered limited protection against S. dysenteriae challenge. Our results show the feasibility of generating a protective Shigella vaccine comprised of the DB fusion.

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“…Those invasion plasmid antigens (Ipas) comprises IpaA, IpaB, IpaC, and IpaD, against which substantial antibody levels have been detected in the sera of experimentally infected monkeys (29) and naturally infected children and adults (26,30,31). Furthermore, Ipas have been shown to be protective in animal studies (32)(33)(34). More recently, a novel and potentially cross-protective protein antigen, termed pan-Shigella surface protein 1 (PSSP1), has been identified on the C terminus of Shigella outer membrane protease IcsP and is conserved among all Shigella species and serotypes (35).…”

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confidence: 99%

Circulating Gut-Homing (α ₄ β ₇ ⁺ ) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea

Sinha

Dey

Saletti

et al. 2016

Clin Vaccine Immunol

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dDeveloping countries are burdened with Shigella diarrhea. Understanding mucosal immune responses associated with natural Shigella infection is important to identify potential correlates of protection and, as such, to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies against highly conserved invasive plasmid antigens (IpaC, IpaD20, and IpaD120) and two recently identified surface protein antigens, pan-Shigella surface protein antigen 1 (PSSP1) and PSSP2, common to all virulent Shigella strains. We examined blood and stool specimens from 37 diarrheal patients admitted to the Infectious Diseases & Beliaghata General Hospital, Kolkata, India. The etiological agent of diarrhea was investigated in stool specimens by microbiological methods and real-time PCR. Gut-homing (␣ 4 ␤ 7 ؉ ) antibodysecreting cells (ASCs) were isolated from patient blood by means of combined magnetic cell sorting and two-color enzymelinked immunosorbent spot (ELISPOT) assay. Overall, 57% (21 of 37) and 65% (24 of 37) of the patients were positive for Shigella infection by microbiological and real-time PCR assays, respectively. The frequency of ␣ 4 ␤ 7 ؉ IgG ASC responders against Ipas was higher than that observed against PSSP1 or PSSP2, regardless of the Shigella serotype isolated from these patients. Thus, ␣ 4 ␤ 7 ؉ ASC responses to Ipas may be considered an indirect marker of Shigella infection. The apparent weakness of ASC responses to PSSP1 is consistent with the lack of cross-protection induced by natural Shigella infection. The finding that ASC responses to IpaD develop in patients with recent-onset shigellosis indicates that such responses may not be protective or may wane too rapidly and/or be of insufficient magnitude.

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Parenteral immunization with IpaB/IpaD protects mice against lethal pulmonary infection by Shigella

Cited by 39 publications

References 33 publications

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

Circulating Gut-Homing (α ₄ β ₇ ⁺ ) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea

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Parenteral immunization with IpaB/IpaD protects mice against lethal pulmonary infection by Shigella

Cited by 39 publications

References 33 publications

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

Circulating Gut-Homing (α 4 β 7 + ) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea

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Circulating Gut-Homing (α ₄ β ₇ ⁺ ) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea