Shigella flexneri vaccine development: Oral administration of peptides derived from the 49.8 kDa pili protein subunit activates the intestinal immune response in mice

Anam, Khoirul; Endharti, Agustina Tri; Poeranto, Sri; Sujuti, Hidayat; Hidayati, Dwi Yuni Nur; Prawiro, Sumarno Reto

doi:10.14202/vetworld.2022.281-287

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…This cytokine induces the release of secretory IgA (sIgA) into the lumen, which was also confirmed in our research. Different groups have reported an increase in IL-17A following vaccination in both mice [33] and humans [29], underscoring the significance of Th1/Th17 cytokine responses as an important indicator of vaccine protective capacity.…”

Section: Discussionmentioning

confidence: 94%

Refining Immunogenicity through Intradermal Delivery of Outer Membrane Vesicles against Shigella flexneri in Mice

Pastor,

Calvo,

Salvador-Erro

et al. 2023

IJMS

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Shigellosis remains a global health concern, especially in low- and middle-income countries. Despite improvements in sanitation, the absence of a licensed vaccine for human use has prompted global health organizations to support the development of a safe and effective multivalent vaccine that is cost-effective and accessible for limited-resource regions. Outer Membrane Vesicles (OMVs) have emerged in recent years as an alternative to live attenuated or whole-inactivated vaccines due to their immunogenicity and self-adjuvating properties. Previous works have demonstrated the safety and protective capacity of OMVs against Shigella flexneri infection in mouse models when administered through mucosal or intradermal routes. However, some immunological properties, such as the cellular response or cross-protection among different Shigella strains, remained unexplored. In this study, we demonstrate that intradermal immunization of OMVs with needle-free devices recruits a high number of immune cells in the dermis, leading to a robust cellular response marked by antigen-specific cytokine release and activation of effector CD4 T cells. Additionally, functional antibodies are generated, neutralizing various Shigella serotypes, suggesting cross-protective capacity. These findings highlight the potential of OMVs as a promising vaccine platform against shigellosis and support intradermal administration as a simple and painless vaccination strategy to address this health challenge.

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Section: Discussionmentioning

confidence: 94%

Refining Immunogenicity through Intradermal Delivery of Outer Membrane Vesicles against Shigella flexneri in Mice

Pastor,

Calvo,

Salvador-Erro

et al. 2023

IJMS

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“…S. flexneri pathogenesis in humans begins with invasion and adhesion to the intestinal epithelial lining, facilitated by its virulence plasmid-encoded Type 3 Secretion System (T3SS), and continued to multiply in the target cell cytoplasm [ 29 ]. Furthermore, Shigella's pili play an important role in the overall bacterial-host pathogenesis [ 30 ]. Shigella species that cause dysentery are distributed worldwide, with S. flexneri being the most frequent in developing countries [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Production of highly immunogenic and safe Triton X-100 produced bacterial ghost vaccine against Shigella flexneri 2b serotype

Abdelfattah,

Samir,

Amin

2023

Gut Pathog

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Background Bacterial ghost cells (BGCs) are cells were drained of their genetic and cytoplasmic components. This work aimed to develop vaccine candidates against the Shigella flexneri (S. flexneri) 2b serotype using the BGCs approach. For the first time, (S. flexneri) 2b serotype BGCs vaccine was prepared by incubation with Triton X-100 (TX100) for only 12 h. Its safety and immunogenicity were compared to another vaccine produced using a previously used surfactant, namely Tween 80 (TW80). Scanning electron microscopy (SEM), cellular DNA, protein contents measurements, and ghost cell re-cultivation were used to confirm the successful generation of the BGCs. Immunogenicity was assessed through mice's intraperitoneal (IP) immunization followed by infection with S. flexneri ATCC 12022. Finally, histopathological examination was carried out. Results Viable colony forming units (CFUs) of S. flexneri were counted from stool samples as well as homogenized colon tissues of the non-immunized challenged group. Immunized mice sera showed a significant increase in serum bactericidal activity of both preparations (TX100 = 40% and TW80 = 56%) compared to the non-immunized challenged group (positive control). The IgG levels of the bacterial ghost-vaccinated groups were four and three times greater for the TX100 and TW80 ghost vaccines, respectively, compared to that of the positive control; both bacterial ghost vaccines (BGVs) were safe and effective, according to the results of the safety check tests and histopathological analysis. Conclusions When comparing the BGVs prepared using TX100 and TW80 methods, the use of TX100 as a new chemical treating agent for BGC production attained robust results in terms of shorter incubation time with the targeted cells and a strong immune response against S. flexneri 2b serotype ATCC 12022 in the IP challenge test. However, a clinical study is needed to confirm the efficacy and total safety of this novel vaccine.

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“…In conclusion, L-DBF is a self-adjuvanting subunit vaccine candidate that can induce a protective immune response against multiple Shigella serotypes and species, regardless of whether the host has had prior Shigella exposure or not. While other subunit vaccines have seen tested ( 33 , 34 ), the inclusion the two essential and surface exposed immunogens of IpaD and IpaB makes this vaccine platform unique. Then the addition LTA1 and its ability to elicit a strong mucosal immune response suggest that L-DBF is an attractive vaccine candidate for use in regions where shigellosis is endemic.…”

Section: Discussionmentioning

confidence: 99%

The L-DBF vaccine cross protects mice against different Shigella serotypes after prior exposure to the pathogen

Lu,

Howlader,

Das

et al. 2023

Microbiol Spectr

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Shigellosis (bacillary dysentery) is a severe diarrheal disease caused by members of the genus Shigella , which results in 90 million cases annually around the world. The Shigella type III secretion system (T3SS) is a specialized secretion system that is the primary virulence factor it uses to infect the colonic mucosa. The type III secretion apparatus (T3SA) proteins IpaB and IpaD, as well as the genetic fusion, DBF, have been demonstrated to protect mice from Shigella spp. infection in a lethal pulmonary model. In a previous study, we fused LTA1, the active moiety of lethal toxin from enterotoxigenic Escherichia coli to DBF to produce a self-adjuvanting vaccine candidate L-DBF, which cross-protected mice against four serotypes of Shigella flexneri and Shigella sonnei . Here, we exposed mice with one or two sublethal doses of S. flexneri 2a to identify whether the immune response induced by L-DBF in the host would be affected by prior infection by homologous or heterologous Shigella serotypes. We demonstrate that pre-infection with two sublethal doses of S. flexneri 2a did not elicit cross-protection against S. sonnei , while vaccination with L-DBF did. Our results indicate that L-DBF is a feasible vaccine candidate that offers cross-protection against Shigella ’s different serotypes even after prior exposure to the pathogen. This work provides a proof of concept that a novel subunit vaccine can not only protect a naïve host from Shigella challenge, but also can protect against challenge after prior infection by the same or different Shigella serotypes. IMPORTANCE Shigellosis is endemic to low- and middle-income regions of the world where children are especially vulnerable. In many cases, there are pre-existing antibodies in the local population and the effect of prior exposure should be considered in the development and testing of vaccines against Shigella infection. Our study shows that L-DBF-induced immune responses are not adversely affected by prior exposure to this pathogen. Moreover, somewhat different cytokine profiles were observed in the lungs of vaccinated mice not having been exposed to Shigella , suggesting that the immune responses elicited by Shigella infection and L-DBF vaccination follow different pathways.

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Shigella flexneri vaccine development: Oral administration of peptides derived from the 49.8 kDa pili protein subunit activates the intestinal immune response in mice

Cited by 7 publications

References 49 publications

Refining Immunogenicity through Intradermal Delivery of Outer Membrane Vesicles against Shigella flexneri in Mice

Refining Immunogenicity through Intradermal Delivery of Outer Membrane Vesicles against Shigella flexneri in Mice

Production of highly immunogenic and safe Triton X-100 produced bacterial ghost vaccine against Shigella flexneri 2b serotype

The L-DBF vaccine cross protects mice against different Shigella serotypes after prior exposure to the pathogen

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