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Transcutaneous immunization of healthy volunteers with an attenuated Listeria monocytogenes vaccine strain and cholera toxin adjuvant.

ABSTRACT: BACKGROUND:Attenuated Listeria monocytogenes vaccine strains have been administered intravenously (Le et al., Maciag et al.) and orally (Angelakopoulos et al., Johnson et al.) to humans. Here, one was given transcutaneously with cholera toxin adjuvant. METHODS:Eight healthy volunteers were studied (5 active, 3 placebo). Safety was assessed by physical exam and labs. Systemic immunological responses were measured by ELISA and IFN-gamma ELISpot. RESULTS:4/5 active volunteers had cellular responses to listerial antigens. 5/5 active volunteers showed humoral responses to cholera toxin. CONCLUSIONS:An attenuated L. monocytogenes vector was safely administered transcutaneously. Topical administration appeared at least as immunogenic as previously studied oral delivery.

SUBMITTER: Eypper EH

PROVIDER: S-EPMC3831363 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Transcutaneous immunization of healthy volunteers with an attenuated Listeria monocytogenes vaccine strain and cholera toxin adjuvant.

Eypper Elizabeth H EH Johnson Paul V PV Purro Eva I EI Hohmann Elizabeth L EL

Vaccine 20130522 32

<h4>Background</h4>Attenuated Listeria monocytogenes vaccine strains have been administered intravenously (Le et al., Maciag et al.) and orally (Angelakopoulos et al., Johnson et al.) to humans. Here, one was given transcutaneously with cholera toxin adjuvant.<h4>Methods</h4>Eight healthy volunteers were studied (5 active, 3 placebo). Safety was assessed by physical exam and labs. Systemic immunological responses were measured by ELISA and IFN-gamma ELISpot.<h4>Results</h4>4/5 active volunteers ...[more]

PMID: 23707162

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Project description:The calcium-binding protein S100A4 has been described to promote pathological inflammation in experimental autoimmune and inflammatory disorders and in allergy and to contribute to antigen presentation and antibody response after parenteral immunization with an alum-adjuvanted antigen. In this study, we extend these findings by demonstrating that mice lacking S100A4 have a defective humoral and cellular immune response to mucosal (sublingual) immunization with a model protein antigen [ovalbumin (OVA)] given together with the strong mucosal adjuvant cholera toxin (CT), and that this impairment is due to defective adjuvant-stimulated antigen presentation by antigen-presenting cells. In comparison to wild-type (WT) mice, mice genetically lacking S100A4 had reduced humoral and cellular immune responses after immunization with OVA plus CT, including a complete lack of detectable germinal center reaction. Further, when stimulated in vitro with OVA plus CT, S100A4-/- dendritic cells (DCs) showed impaired responses in several CT-stimulated immune regulatory molecules including the co-stimulatory molecule CD86, inflammasome-associated caspase-1 and IL-1β. Coculture of OVA-specific OT-II T cells with S100A4-/- DCs that had been pulse incubated with OVA plus CT resulted in impaired OT-II T cell proliferation and reduced production of Th1, Th2, and Th17 cytokines compared to similar cocultures with WT DCs. In accordance with these findings, transfection of WT DCs with S100A4-targeting small interfering RNA (siRNA) but not mock-siRNA resulted in significant reductions in the expression of caspase-1 and IL-1β as well as CD86 in response to CT. Importantly, also engraftment of WT DCs into S100A4-/- mice effectively restored the immune response to immunization in the recipients. In conclusion, our results demonstrate that deficiency in S100A4 has a strong impact on the development of both humoral and cellular immunity after mucosal immunization using CT as adjuvant.

Dataset Information

Transcutaneous immunization of healthy volunteers with an attenuated Listeria monocytogenes vaccine strain and cholera toxin adjuvant.

Publications

Transcutaneous immunization of healthy volunteers with an attenuated Listeria monocytogenes vaccine strain and cholera toxin adjuvant.

Similar Datasets

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