A tetravalent Shigella outer membrane vesicles based candidate vaccine offered cross-protection against all the serogroups of Shigella in adult mice

Bhaumik, Ushasi; Halder, Prolay; Howlader, Debaki Ranjan; Banerjee, Shreya; Maiti, Suhrid; Koley, Hemanta

doi:10.1016/j.micinf.2023.105100

Cited by 9 publications

(5 citation statements)

References 45 publications

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“…As previously mentioned, in line with WHO recommendations, the development of a multivalent Shigella vaccine is crucial to protect against the most prevalent Shigella serotypes, including S. flexneri 2a, 3a, 6 and S. sonnei [25]. Several works with Shigella OMV-vaccine candidates have demonstrated cross-protection against these serogroups in mice when orally or intraperitoneally administered [26,27]. Here, we show for the first time that sera obtained from our OMV complex exhibit cross-neutralizing capacity against different Shigella serotypes, and while this finding has to be further confirmed in animal models, it is a promising correlate of protection.…”

Section: Discussionmentioning

confidence: 82%

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: 82%

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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“…Thus, we have developed an OMVs-based vaccine candidate against Campylobacter jejuni, Salmonella Typhimurium and Salmonella Enteritidis, which can provide combined broad-spectrum protective immunity against infections caused by these pathogens. Neisseria, Shigella and Salmonella species OMVs have already been used as potent immunogens [50][51][52][53]. Previously, 25 µg intramuscular administration of N. meningitis OMV vaccine (MenBvac and MeNZB) was reported to effectively elicit protective immunity [54,55].…”

Section: Discussionmentioning

confidence: 99%

“…Previously, our studies showed OMVs isolated from Shigella sp. [51], Vibrio cholerae [69] and Salmonella Typhi and Salmonella Paratyphi A [40] confer protection against these pathogens. TOMVs-immunized mice colons displayed signi cantly lower histopathological scores than non-immunized mice colons.…”

Section: Discussionmentioning

confidence: 99%

Trivalent outer membrane vesicles-based combination vaccine candidate induces protective immunity against Campylobacter and invasive non-typhoidal Salmonella in adult mice

Banerjee,

Halder,

Das

et al. 2024

Preprint

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Campylobacter and non-typhoidal Salmonella (NTS) are among the most common causative agents of gastroenteritis worldwide. As of now, no single combination licensed vaccine is available for public health use against both NTS and Campylobacterspecies. Outer-membrane vesicles (OMVs) are nanoscale proteoliposomes released from the surface of gram-negative bacteria during log phase and harbor a variety of immunogenic proteins. Based on epidemiology of infections, we formulated a novel trivalent outer membrane vesicles (TOMVs)-based vaccine candidate against Campylobacter jejuni (CJ),Salmonella Typhimurium (ST) andSalmonella Enteritidis (SE). Isolated OMVs from CJ, ST and SE were combined in equal ratios for formulation of TOMVs and 5 µg of the developed vaccine candidate was used for intraperitoneal immunization of adult BALB/c mice. Immunization with TOMVs significantly activated both the humoral and cellular arm of adaptive immune response. Robust bactericidal effect was elicited by TOMVs immunized adult mice sera. TOMVs immunization induced long-term protective efficacy against CJ, ST and SE infections in mice. The study illustrates the ability of TOMVs-based combination immunogen in eliciting broad-spectrum protective immunity against prevalent Campylobacter and NTS pathogens. According to the findings, TOMVs can work as a potent combination-based acellular vaccine candidate for amelioration of Campylobacter and NTS-mediated gastroenteritis.

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“…Outer membrane vesicles (OMVs) were isolated from the Helicobacter strain [A61C (1), cagA+,vacAs1m1 ] following the methods described by Bhaumik et al, 2023, with slight modification [26]. In brief, BB broth (BD, Difco, USA) was inoculated with log phase (OD600 ∼0.6) preculture of the respective strains and kept overnight in microaerophilic conditions under constant shaking (120 rpm) at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Establishment of an intragastric surgical model using C57BL/6 mice to study the vaccine efficacy of OMV-based immunogens againstHelicobacter pylori

Das,

Halder,

Banerjee

et al. 2023

Preprint

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Chronic gastritis is one of the major symptoms of gastro-duodenal disorders typically induced byHelicobacter pylori(H. pylori).To date, no suitable model is available to study pathophysiology and therapeutic measures accurately. Here, we have presented a successful surgical infection model ofH. pylori-induced gastritis in C57BL/6 mice that resembles features similar to human infection. The proposed model does not require any preparatory treatment other than surgical intervention. C57BL/6 mice were injected with wild-type SS1 (Sydney strain 1, reference strain) directly into the stomach. Seven days post infection, infected animals showed alterations in cytokine responses along with inflammatory cell infiltration in the lamina propria, depicting a prominent inflammatory response due to infection. To understand the immunogenicity and protective efficacy, the mice were immunized with outer membrane vesicles (OMVs) isolated from an indigenous strain with putative virulence factors ofH. pylori[A61C (1),cag+/vacA s1m1]. In contrast to the nonimmunized cohort, the OMV-immunized cohort showed a gradual increase in serum immunoglobulin(s) levels on the 35thday after the first immunization. This conferred protective immunity against subsequent challenge with the reference strain (SS1). Direct inoculation ofH. pyloriinto the stomach influenced infection in a short time and, more importantly, in a dose-dependent manner, indicating the usefulness of the developed model for pathophysiology, therapeutic and prophylactic studies.

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A tetravalent Shigella outer membrane vesicles based candidate vaccine offered cross-protection against all the serogroups of Shigella in adult mice

Cited by 9 publications

References 45 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

Trivalent outer membrane vesicles-based combination vaccine candidate induces protective immunity against Campylobacter and invasive non-typhoidal Salmonella in adult mice

Establishment of an intragastric surgical model using C57BL/6 mice to study the vaccine efficacy of OMV-based immunogens againstHelicobacter pylori

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