A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses

Ibáñez, Andrés; Coria, Lorena M.; Carabajal, Marianela V.; Delpino, M. Victoria; Risso, Gabriela Sofía; Cobiello, Paula Gonzalez; Rinaldi, Jimena; Barrionuevo, Paula; Bruno, Luciana; Frank, Fernanda M.; Klinke, S.; Goldbaum, Fernando A.; Briones, Gabriel; Giambartolomei, Guillermo H.; Pasquevich, Karina A.; Cassataro, Juliana

doi:10.1016/j.jconrel.2015.10.011

Cited by 23 publications

(47 citation statements)

References 40 publications

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“…The Toxoplasma gondii serine protease inhibitor TgPI-1 elicited high titers of IgG antibodies and induced a mixed Th1/Th2 immunological response, with significant production of IFN-γ, when evaluated as a vaccine candidate ( 41 , 42 ). Another serine protease inhibitor present in the intracellular bacteria Brucella abortus , the protein Omp-19, when evaluated as a vaccine candidate, elicited a Th1 immunological response when administrated intraperitoneally, and a mixed Th1/Th17 immunological profile but when administrated orally ( 43 , 44 ). Finally, Ancylostoma ceylanicum Kunitz-type inhibitor (AceKI), also elicited significant titers of IgG in a murine model ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni SmKI-1 or Its C-Terminal Fragment Induces Partial Protection Against S. mansoni Infection in Mice

et al. 2018

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Current schistosomiasis control strategies are mainly based on chemotherapy, but the development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. When it comes to vaccine candidates, several genes encoding Schistosoma mansoni proteins expressed at the mammalian host–parasite interface have been tested. Among the most promising molecules are the proteins present on the tegument and digestive tract of the parasite. In this study, we evaluate the potential of SmKI-1, the first Kunitz-type protease inhibitor functionally characterized in S. mansoni, as a vaccine candidate. Bioinformatic analysis points to the C-terminal fragment as the main region of the molecule responsible for the development of a potential protective immune response induced by SmKI-1. Therefore, for the vaccine formulations, we produced the recombinant (r) SmKI-1 and two different fragments, its Kunitz (KI) domain and its C-terminal tail. First, we demonstrate that mice immunized with recombinant SmKI-1 (rSmKI-1) or its fragments, formulated with Freund’s adjuvant, induced the production of IgG-specific antibodies. Further, all vaccine formulations tested here also induced a Th1-type of immune response, as suggested by the production of IFN-γ and TNF-α by protein-stimulated cultured splenocytes. However, the protective effect conferred by vaccination was only observed in groups which received rSmKI-1 or C-terminal domain vaccines. Mice administered with rSmKI-1 demonstrated reduction of 47% in worm burden, 36% in egg number in mouse livers, and 33% in area of liver granulomas. Additionally, mice injected with C-terminal domain showed reduction of 28% in worm burden, 38% in egg number in liver, and 25% in area of liver granulomas. In contrast, KI domain immunization was unable to reduce worm burden and ameliorate liver pathology after challenge infection. Taken together, our data demonstrated that SmKI-1 is a potential candidate for use in a vaccine to control schistosomiasis, and its C-terminal tail seems to be the main region of the molecule responsible for protection conferred by this antigen.

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Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni SmKI-1 or Its C-Terminal Fragment Induces Partial Protection Against S. mansoni Infection in Mice

et al. 2018

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“…Outside chemically based delivery systems, viral and bacterial Ags expressed in safe natural carriers such as probiotic strains generate specific local and systemic protective immunity observed in case of S. Typhimurium infection in mice when fed orally (223)(224)(225)(226). Another manner to contribute to the good delivery of Ags in the intestinal mucosa would consist of orally coadministering the vaccine formulation with the protease inhibitor U-Omp19 from Brucella, which has been shown both to increase the half-life of Ags delivered along the GI tract and to activate APCs (227). Recently, NPs have been formulated to overcome the challenging environment encountered along the oral route of administration; such a formulation called single multiple pill (SmPill) combines whole-cell killed Escherichia coli overexpressing the colonization factor Ag I in a dispersed phase, ␣-galactosylceramide as an adjuvant, and a polymer coating preventing gastric degradation (228).…”

Section: Delivery Vehicles For Mucosal Vaccinationmentioning

confidence: 99%

Vaccination against Salmonella Infection: the Mucosal Way

Gayet¹,

Bioley²,

Rochereau³

et al. 2017

Microbiol Mol Biol Rev

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subspecies includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy.

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“…Immune protective responses were independent of TLR4. Also, U-Omp19 co-delivered orally induces specific mucosal immune responses [9][10][11]. All together these results prompted us to test the hypothesis that U-Omp19 is an adjuvant for co-administered Ags when delivered subcutaneously.…”

Section: Introductionmentioning

confidence: 99%

Brucella abortus Omp19 recombinant protein subcutaneously co-delivered with an antigen enhances antigen-specific T helper 1 memory responses and induces protection against parasite challenge

Coria

Ibáñez

Pasquevich

et al. 2016

Vaccine

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The discovery of effective adjuvants for many vaccines especially those with limited commercial appeal, such as vaccines to poverty-related diseases, is required. In this work, we demonstrated that subcutaneous co-administration of mice with the outer membrane protein U-Omp19 from Brucella spp. plus OVA as antigen (Ag) increases Ag-specific T cell proliferation and T helper (Th) 1 immune responses in vitro and in vivo. U-Omp19 treated dendritic cells promote IFN-γ production by specific CD4(+) T cells and increases T cell proliferation. U-Omp19 co-administration induces the production of Ag specific effector memory T cell populations (CD4(+) CD44(high) CD62L(low) T cells). Finally, subcutaneous co-administration of U-Omp19 with Trypanosoma cruzi Ags confers protection against virulent parasite challenge, reducing parasitemia and weight loss while increasing mice survival. These results indicate that the bacterial protein U-Omp19 when delivered subcutaneously could be a suitable component of vaccine formulations against infectious diseases requiring Th1 immune responses.

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A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses

Cited by 23 publications

References 40 publications

Schistosoma mansoni SmKI-1 or Its C-Terminal Fragment Induces Partial Protection Against S. mansoni Infection in Mice

Schistosoma mansoni SmKI-1 or Its C-Terminal Fragment Induces Partial Protection Against S. mansoni Infection in Mice

Vaccination against Salmonella Infection: the Mucosal Way

Brucella abortus Omp19 recombinant protein subcutaneously co-delivered with an antigen enhances antigen-specific T helper 1 memory responses and induces protection against parasite challenge

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