Transcutaneous Immunization with Combined Cholera Toxin and CpG Adjuvant Protects against<i>Chlamydia muridarum</i>Genital Tract Infection

Berry, Linda J.; Hickey, Danica K.; Skelding, Kathryn A.; Bao, Shisan; Rendina, Amanda M.; Hansbro, Philip M.; Gockel, Christine M.; Beagley, Kenneth W.

doi:10.1128/iai.72.2.1019-1028.2004

Cited by 135 publications

(117 citation statements)

References 67 publications

(30 reference statements)

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“…This fusion peptide (OVA 257-280 , SIINFEKLTEWTSSNVMEERKIKV) mimics the naturally occurring adjacent sequence order of the CTL and Th epitope (H-2K b MHC class I epitope, 257 SIINFEKL 264 ; I-A b MHC class II epitope, 265 TEWTSSNVMEERKIKV 280 38 ). The E7 multiepitope peptide (E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] , QAEPDRAHYNIVTFCCKCD) comprises 3 different epitopes in an overlapping form: the H-2D b MHC class I epitope 49 RAHYNIVTF 57 , the I-A and I-E MHC class II epitope 48 DRA-HYNIVTF 57 and the linear panspecific B-cell epitope 44 QAEPD 48 . 39 Alternatively, mice were immunized with an E7 single epitope peptide (E7 [49][50][51][52][53][54][55][56][57] ) encompassing only the E7 CTL sequence ( 49 RAHYNIVTF 57 ).…”

Section: Peptides Proteins and Adjuvantsmentioning

confidence: 99%

“…The vaccine (35 ll) was applied onto the bare skin and left for 30 min before removing with tap water. Mice were transcutaneously immunized either with peptides (OVA 257-280 and E7 [49][50][51][52][53][54][55][56][57] , 100 lg/mouse; E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] , 200 lg/mouse) or with proteins (OVA and E7, 100 lg/mouse) dissolved in PBS/DMSO with or without CT (in PBS, 50 lg/mouse) and CpG (in HPLC-purified water, 100 lg/mouse) as adjuvants. For s.c. immunization, peptides were dissolved in PBS, mixed 1:1 with TM according to the manufacturer's recommendation and applied into the tail base.…”

Section: Immunizationsmentioning

confidence: 99%

“…Mice were immunized transcutaneously 3 times in biweekly intervals either with 200 lg E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] peptide and CT/CpG or with CT/CpG alone or were left untreated. Nine days after the last boost, mice were challenged s.c. into the right flank with 5 3 10 5 C3 cells in 100 ll PBS under isoflurane anesthesia.…”

Section: Tumor Protectionmentioning

confidence: 99%

“…Mice were immunized according to the optimized TCI protocol (3 3 TCI including CT/CpG as adjuvants). Mice received 100 lg E7 [49][50][51][52][53][54][55][56][57] or 200 lg E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] (equimolar to E7 [49][50][51][52][53][54][55][56][57] ) plus CT/CpG. Positive controls were immunized s.c. with E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]...…”

Section: Tci With An Hpv-16 E7 Multiepitope Peptide In Combination Wimentioning

confidence: 99%

“…After 2 rounds of in vitro restimulation, mice immunized with E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] peptide plus adjuvants either by TCI or s.c. showed significant E7-specific cytotoxic activity at an effector to target ratio of 20 (TCI 16%, 23%, 12%; s.c. pooled cells from all 3 mice 42%; data not shown). E7-specific lysis in the TCI group further increased after an additional round of in vitro restimulation to 35%, 52% and 14%, respectively (Fig.…”

Section: Tci With An Hpv-16 E7 Multiepitope Peptide In Combination Wimentioning

confidence: 99%

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Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

2006

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Previous reports have shown that transcutaneous immunization (TCI) with proteins or peptides in combination with adjuvants efficiently induces specific cellular and humoral immune responses. However, depending on the kind of skin pretreatment, induction of cellular immune responses was restricted to generation of either specific cytotoxic T lymphocytes (CTLs) or T-helper (Th) cells. In this study, we induced antigen-specific CTL responses together with the appropriate Th responses by TCI of C57BL/6 mice. We applied ovalbumin protein or an ovalbuminderived fusion peptide containing a CTL and Th epitope together with a combination of cholera toxin (CT) and CpG oligodeoxynucleotide (CpG) onto cold wax-depilated and hydrated bare skin. TCI with the ovalbumin fusion peptide induced more robust CTL and Th responses than that with ovalbumin protein. The fusion peptide in combination with the nontoxic CT derivative CTA1-D2D1 and CpG induced an antigen-specific CTL response, albeit less efficiently than in combination with complete CT. Further, we compared the potency of HPV-16 E7 oncoprotein-derived peptides containing single (CTL) or multiple (CTL 1 Th 1 B cell) epitopes to induce effective CTL responses. Strong E7-specific CTL responses were detected only after TCI with the E7 multiepitope peptide. This peptide was also shown to protect mice against tumor growth after challenge with HPV-16 E7-positive tumor cells. TCI with E7 protein and CT/CpG led to formation of an E7-specific humoral immune response. ' 2005 Wiley-Liss, Inc.Key words: transcutaneous immunization; human papillomavirus type 16 E7 (HPV-16 E7); CTA1-D2D1; cytotoxic T lymphocyte; T helper cell; ovalbumin; tumor protection TCI is a novel strategy in modern vaccinology. By this application, blood-borne transmission of diseases through the reuse of needles, which is a common practice in remote parts of the world, can be circumvented and better compliance of vaccinees obtained. Apart from its benefits toward vaccine safety, TCI targets LCs, a dense population of highly accessible APCs within the skin. 1 An important feature of vaccination against viral infections and virus-based tumors is the induction of CTLs. 2-4 Upon activation by APCs, predominantly DCs, CTLs are able to selectively kill antigen-expressing cells. 5 For clearance of certain viral infections, the aid of Th cells for CTL activation is necessary. 6 The bias to one of the 2 Th subsets (Th1 > Th2) is a prerequisite for specific CTL induction. 7 Generation of specific CTLs against proteinaceous or peptidebased vaccines in combination with adjuvants after TS of the skin is possible. 8-10 TS leads to removal of the outermost horny layer of the skin, resulting in enhanced permeability and maturation and activation of LCs via inflammatory cytokines secreted from keratinocytes. 11,12 The barrier function of the SC can also be bypassed by hydration of the skin, which leads to swelling of the keratinocytes and pooling of fluid into intercellular spaces. This kind of pretreatment of the skin leads to ...

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Section: Peptides Proteins and Adjuvantsmentioning

confidence: 99%

Section: Immunizationsmentioning

confidence: 99%

Section: Tumor Protectionmentioning

confidence: 99%

Section: Tci With An Hpv-16 E7 Multiepitope Peptide In Combination Wimentioning

confidence: 99%

Section: Tci With An Hpv-16 E7 Multiepitope Peptide In Combination Wimentioning

confidence: 99%

See 3 more Smart Citations

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

2006

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Transcutaneous Immunization via Vaccine Patch Delivery System

Seid¹,

Glenn²

2012

Vaccinology

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Chlamydia Trachomatis Urogenital Infections

Armitage

Carey

Hickey

et al. 2018

Diagnostics to Pathogenomics of Sexually Transmitted Infections

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Quantitative evaluation of the cells involved in the immune system, such as lymphocytes, plasma cells, macrophages, dendritic cells, and epithelial cells, together with their products, including antibodies, cytokines, and humoral factors of innate immunity, convincingly revealed that the immune system associated with the mucosae is greater than its systemic counterpart (Russell et al. 2015a). This fact should not be surprising, as the development of the entire immune system during evolution and continuously in everyday life is driven by stimulation with commensal microbiota, antigens present in food and inhaled air, as well as pathogens throughout the enormous surface area of mucosal sites, which far exceeds the skin surface. The mucosal immune system comprises anatomically remote and physiologically distinct compartments that provide protection at various mucosal sites. Although the genital tract shares some common features with other mucosae, including the presence of humoral factors and cells of innate immunity, and the origin of cells involved in antibody production and T cell-mediated immunity, there are also many distinct features characteristic of the genital tract (Russell and Mestecky 2002, 2010; Mestecky et al. 2005). The spectrum of antigens including commensal or pathogenic microorganisms, and sperm is different from those at other mucosal sites. Furthermore, the primary physiological role of the genital tract is reproduction, which involves the acceptance of allogeneic sperm and semi-allogeneic offspring. This distinct physiological role influences the immune system of the genital tract with respect to the induction or suppression of immune responses, which must be considered in the development and application of vaccines against infectious agents of sexually transmitted diseases.

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Transcutaneous Immunization with Combined Cholera Toxin and CpG Adjuvant Protects againstChlamydia muridarumGenital Tract Infection

Cited by 135 publications

References 67 publications

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

Transcutaneous Immunization via Vaccine Patch Delivery System

Chlamydia Trachomatis Urogenital Infections

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