A Novel
            <i>Shigella</i>
            O-Polysaccharide–IpaB Conjugate Vaccine Elicits Robust Antibody Responses and Confers Protection against Multiple
            <i>Shigella</i>
            Serotypes

Desalegn, Girmay; Kapoor, Neeraj; Pill-Pepe, Lucy; Bautista, Leslie; Yin, Lu; Ndungo, Esther; Oaks, Edwin V.; Fairman, Jeff; Pasetti, Marcela F.

doi:10.1128/msphere.00019-23

Cited by 8 publications

(7 citation statements)

References 45 publications

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“…An unexpected finding was the low (negligible) VirGα-specific serum IgG responses in mice immunized IN with sublethal doses of S. flexneri 2a and S. sonnei (Fig. 2b ), while these controls developed robust serum IgG responses to the OPS of the respective immunizing strain 24 . VirGα-specific IgA responses were detected neither in serum or feces of mice immunized with VirGα via IM, nor in those that received sublethal IN doses of S. flexneri 2a and S. sonnei (data not shown).…”

Section: Resultsmentioning

confidence: 96%

“…A polyvalent fusion protein containing epitopes from IpaB, IpaD, VirG, GuaB and Shiga toxins has been shown to elicit broadly functional antibodies and cross-protection against S. sonnei and S. flexneri serotypes 27 . Our group developed a Shigella OPS-IpaB conjugate vaccine candidate capable of eliciting cross-protective immunity in mice 24 . IpaB and VirG are appealing vaccine targets because of their immunogenic properties and association with protective immunity in humans 43 , 44 , 58 .…”

Section: Discussionmentioning

confidence: 99%

“…E. coli DH5α and BL21 (DE3) pLysS cells were cultured in LB media at 37 °C. S. flexneri 2a 2457T and S. sonnei Moseley were prepared as previously described 19 , 24 . Briefly, the strains were streaked on tryptic soy agar (TSA) containing 0.02% Congo red and grown overnight at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Blood collection and challenges were performed under Isoflurane anesthesia (with oxygen) dispensed through a precision vaporizer (VetEquip, Inc., Pleasanton, CA). Infected mice were monitored daily for 15 days as previously described 19 , 24 . Animals overtly sick with >20% weight loss were promptly euthanized.…”

Section: Methodsmentioning

confidence: 99%

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Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate

Desalegn,

Tamilselvi,

Lemme-Dumit

et al. 2024

npj Vaccines

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Diarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, and those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is caused by multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the Shigella virulence factor VirG (or IcsA) and clinical protection in infected individuals. VirG is highly conserved among Shigella strains and appealing as a broad-spectrum vaccine candidate. In this study, we investigated the immunogenicity and protective capacity of VirG as a subunit vaccine in mice. The surface-exposed alpha (α) domain of VirG (VirGα) was produced as a recombinant protein. This region has almost identical immune reactivity to full-length VirG. Administered intramuscularly with alum, VirGα elicited robust immune responses and high protective efficacy against S. flexneri 2a and S. sonnei. Almost complete protection was afforded by VirGα given intranasally with the E. coli double mutant heat-labile toxin (dmLT). VirGα-specific antibodies recognized VirG expressed on live Shigella, and blocked Shigella adhesion and invasion to human colonic cells. These results show for the first time that VirGα is a promising cross-protective vaccine candidate to prevent Shigella infection.

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Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate

Desalegn,

Tamilselvi,

Lemme-Dumit

et al. 2024

npj Vaccines

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“…Studies conducted in Shigella -infected Swedish patients reported that anti-LPS and anti-Ipa immunoglobulin G (IgG) responses are good indicators of recent and previous infections, respectively [ 7 ]. Invasion plasmid B (IpaB) appears to be a particularly well-conserved and immunogenic antigen, and antibodies to IpaB are a potential correlate of protection [ 8 , 9 ]. An association between higher levels of IgG1 antibodies with previous exposure to Shigella and lower risk of developing symptomatic infection was shown in a study conducted in the Israeli Defense Force using the double antibody sandwich enzyme-linked immunosorbent assay (ELISA) [ 10 ].…”

Section: Natural Immunity To Shigella Infectio...mentioning

confidence: 99%

Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study

Benedicto-Matambo,

Avolio,

Badji

et al. 2024

Open Forum Infectious Diseases

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Background Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)–based microbiologic end points for vaccine trials. Methods We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated. Conclusions The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates.

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A multi-epitope protein vaccine encapsulated in alginate nanoparticles as a candidate vaccine against Shigella sonnei

Hashemi,

Osanloo,

Farjadfar

et al. 2024

Sci Rep

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Shigellosis, caused by the Gram-negative bacterium Shigella , is a major global health challenge. Despite extensive research over the past two decades, no commercial vaccine is available to prevent Shigella infection. Developing multi-epitope vaccines offers a promising and innovative approach to tackling infectious diseases. In this study, we produced a multi-epitope vaccine candidate using E. coli BL21 (DE3) plysS bacteria and purified the vaccine protein with Ni-NTA affinity chromatography. We then prepared alginate nanoparticles containing the vaccine protein, with a particle size of 122 ± 6 nm, PDI 0.17, SPAN 0.83, and zeta potential of -27 ± 2 mV. Successful protein loading was confirmed through nanodrop and ATR-FTIR analyses. To evaluate the immunogenicity of the encapsulated vaccine, mice were orally vaccinated, and their serum was analyzed for IgG, IL-4, and IFN-γ levels cytokines. The results showed a significant increase in IgG level in the vaccinated group compared to controls. Additionally, the vaccinated group exhibited a notable increase in IL-4 and IFN-γ cytokines, indicating a robust Th-cell-mediated immune response essential for combating Shigella . Our nano-vaccine demonstrated high efficacy in activating both humoral and cellular immunity, effectively protecting against the bacteria. The alginate-based oral vaccine candidate thus emerges as a promising strategy for developing a multi-epitope vaccine candidate against Shigella .

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A Novel Shigella O-Polysaccharide–IpaB Conjugate Vaccine Elicits Robust Antibody Responses and Confers Protection against Multiple Shigella Serotypes

Cited by 8 publications

References 45 publications

Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate

Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate

Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study

A multi-epitope protein vaccine encapsulated in alginate nanoparticles as a candidate vaccine against Shigella sonnei

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