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| 2. |
- Cuburu, Nicolas, et al.
(författare)
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Sublingual immunization induces broad-based systemic and mucosal immune responses in mice.
- 2007
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 25:51, s. 8598-610
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The potential of sublingual (s.l.) delivery of vaccine was examined in mice. We show the existence of a dense network of dendritic cells (DCs) in the s.l. epithelium and a rapid and transient increase in the frequency of s.l. DCs after topical application of cholera toxin (CT) adjuvant under the tongue. S.l. immunization with ovalbumin and CT induced vigorous systemic and mucosal antibody responses. Such treatment promoted mixed Th1 and Th2 cytokine responses and induced cytotoxic CD8(+) T cells in lung tissues and in systemic lymphoid organs. S.l. immunization was comparable to intranasal immunization and was superior to oral immunization regarding the magnitude and anatomic dissemination of the induced immune responses. S.l. administration of live influenza virus at a dose lethal by the nasal route was well tolerated and did not redirect virus to the olfactory bulb. These features underscore the potential of the s.l. mucosa to serve as an alternative vaccine delivery route.
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| 3. |
- Cuburu, Nicolas, et al.
(författare)
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Sublingual immunization with nonreplicating antigens induces antibody-forming cells and cytotoxic T cells in the female genital tract mucosa and protects against genital papillomavirus infection.
- 2009
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 183:12, s. 7851-9
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Tidskriftsartikel (refereegranskat)abstract
- We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8(+) cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT) as an adjuvant. Sublingual administration of OVA and CT induced Ag-specific IgA and IgG Abs in blood and in cervicovaginal secretions. These responses were associated with large numbers of IgA Ab-secreting cells (ASCs) in the genital mucosa. Genital ASC responses were similar in magnitude and isotype distribution after s.l., intranasal, or vaginal immunization and were superior to those seen after intragastric immunization. Genital, but not blood or spleen, IgA ASC responses were inhibited by treatment with anti-CCL28 Abs, suggesting that the chemokine CCL28 plays a major role in the migration of IgA ASC progenitors to the reproductive tract mucosa. Furthermore, s.l. immunization with OVA induced OVA-specific effector CD8(+) cytolytic T cells in the genital mucosa, and these responses required coadministration of the CT adjuvant. Furthermore, s.l. administration of human papillomavirus virus-like particles with or without the CT adjuvant conferred protection against genital challenge with human papillomavirus pseudovirions. Taken together, these findings underscore the potential of s.l. immunization as an efficient vaccination strategy for inducing genital immune responses and should impact on the development of vaccines against sexually transmitted diseases.
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| 4. |
- Czerkinsky, Cecil, 1953, et al.
(författare)
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Mucosal Delivery Routes for Optimal Immunization: Targeting Immunity to the Right Tissues
- 2012
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Ingår i: Mucosal Vaccines: Modern Concepts, Strategies, and Challenges. - Berlin, Heidelberg : Springer. - 9783642236938 ; , s. 1-18
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Bokkapitel (refereegranskat)abstract
- The mucosal immune system exhibits a high degree of anatomic compartmentalization related to the migratory patterns of lymphocytes activated at different mucosal sites. The selective localization of mucosal lymphocytes to specific tissues is governed by cellular "homing" and chemokine receptors in conjunction with tissue-specific addressins and epithelial cell-derived chemokines that are differentially expressed in "effector" tissues. The compartmentalization of mucosal immune responses imposes constraints on the selection of vaccine administration route. Traditional routes of mucosal immunization include oral and nasal routes. Other routes for inducing mucosal immunity include the rectal, vaginal, sublingual, and transcutaneous routes. Sublingual administration is a new approach that results in induction of mucosal and systemic T cell and antibody responses with an exceptionally broad dissemination to different mucosae, including the gastrointestinal and respiratory tracts, and the genital mucosa. Here, we discuss how sublingual and different routes of immunization can be used to generate immune responses in the desired mucosal tissue(s).
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| 5. |
- Czerkinsky, Cecil, 1953, et al.
(författare)
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Vaccines against enteric infections for the developing world
- 2015
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Ingår i: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 370:1671
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Forskningsöversikt (refereegranskat)abstract
- Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: - limited knowledge regarding the properties of the gut immune system during early life; - lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; - limited knowledge of the factors contributing to oral vaccine under-performance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics.
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| 6. |
- George-Chandy, Annie, 1969, et al.
(författare)
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Oral tolerance induction by mucosal administration of cholera toxin B-coupled antigen involves T-cell proliferation in vivo and is not affected by depletion of CD25+ T cells.
- 2006
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 118:3, s. 311-20
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Tidskriftsartikel (refereegranskat)abstract
- Oral administration of antigens coupled to the B subunit of the cholera toxin (CTB) can dramatically reduce the amount of antigen needed for tolerance induction and has been used in several animal models to suppress conditions where the immune system overreacts to foreign and self-antigens. In this study, the cellular events following oral administration of CTB-coupled antigen was investigated. As a model system, limited numbers of CSFE-labelled cells from influenza haemagglutinin peptide (HApep) T-cell transgenic mice were transferred to wild type mice and the mice were then given CTB-coupled HApep orally. The inductive events of CTB-induced tolerance was characterized by extensive proliferation of HApep-specific T cells in the mesenteric lymph nodes (MLNs) and in the spleen. The proliferating cells up-regulated the gut homing molecule alpha4beta7 and down-regulated the high endothelial venule binding molecule L-selectin. Addition of the whole cholera toxin (CT) to CTB-HApep showed a similar pattern as CTB-HApep feeding, with antigen-specific proliferation in the MLN and spleen and expression of alpha4beta7 on the proliferating cells. However, addition of CT to CTB-HApep, produced a stronger and faster proliferative response and abrogated CTB-HA mediated oral tolerance. Feeding of CTB-HApep expanded CD25+ cells in the MLNs. CTB-induced oral tolerance could, however, not be explained by CD25+ dependent regulatory activity, as oral administration of CTB-HApep to mice depleted of CD25+ cells still gave rise to systemic tolerance. Thus, several mechanisms might co-orchestrate the systemic tolerance seen in response to feeding with CTB-coupled antigen.
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| 7. |
- Holmgren, Jan, 1944, et al.
(författare)
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Mucosal immunity and vaccines
- 2005
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 11:4
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Forskningsöversikt (refereegranskat)
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| 8. |
- Kang, S S, et al.
(författare)
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Anti-bacterial and anti-toxic immunity induced by a killed whole-cell-cholera toxin B subunit cholera vaccine is essential for protection against lethal bacterial infection in mouse pulmonary cholera model.
- 2013
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 6:4, s. 826-37
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Tidskriftsartikel (refereegranskat)abstract
- The lack of appropriate animal model for studying protective immunity has limited vaccine development against cholera. Here, we demonstrate a pulmonary cholera model conferred by intranasal administration of mice with live Vibrio cholerae. The bacterial components, but not cholera toxin, caused lethal and acute pneumonia by inducing massive inflammation. Intranasal immunization with Dukoral, comprising killed whole bacteria and recombinant cholera toxin B subunit (rCTB), developed both mucosal and systemic antibody responses with protection against the lethal challenge. Either rCTB-free Dukoral or rCTB alone partially protected the mice against the challenge. However, reconstitution of rCTB-free Dukoral with rCTB restored full protection. Parenteral immunization with Dukoral evoked strong systemic immunity without induction of mucosal immunity or protection from the challenge. These results suggest that both anti-bacterial and anti-toxic immunity are required for protection against V. cholerae-induced pneumonia, and this animal model is useful for pre-clinical evaluation of candidate cholera vaccines.Mucosal Immunology advance online publication 28 November 2012; doi:10.1038/mi.2012.121.
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