Transcutaneous immunization induces mucosal and systemic immunity: a potent method for targeting immunity to the female reproductive tract

Gockel, Christine M.

doi:10.1016/s0161-5890(00)00074-2

Cited by 85 publications

(43 citation statements)

References 22 publications

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“…However, the observed antisTat IgA responses were modest compared to the serum anti-sTat IgG titers. This could reflect lower antigen presentation by the reproductive antigen-presenting cells due to the estrous cycle of animals, which is known to affect antibody levels in vaginal lavage fluids [33,34]. Although we did not stage the animals for the day of estrous cycle, we collected vaginal washes on 2 consecutive days to minimize the effect of the estrous cycle.…”

Section: Discussionmentioning

confidence: 99%

“…It is composed of 86-101 amino acid residues (depending on the isolate) encoded by two exons. The first 72 amino acid residues (encoded by the first exon) are organized into three functional domains: (i) an acidic N-terminal region (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] that binds to cell surface CD26 and is thought to mediate immunosuppressive activity [3]; (ii) a cysteine-rich domain (aa [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] that mediates binding to chemokine receptors [4]; and (iii) the basic domain (aa 41-60). The latter domain is responsible for the internalization of extracellular Tat and its import into the nucleus and is also required for binding to short RNA transcripts containing the viral transactivation-responsive element (TAR) [5,6].…”

Section: Introductionmentioning

confidence: 99%

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A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

et al. 2004

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The HIV‐1 Tat protein plays a critical role in the pathogenesis of HIV and has been considered as a candidate vaccine antigen. In an effort to design a non‐invasive vaccination strategy against HIV‐1 that stimulates the induction of systemic and mucosal immune responses, we studied the transcutaneous delivery of a synthetic Tat protein using cholera toxin as an adjuvant. Following immunization of BALB/c mice with various doses of Tat, IgG and IgA antibody responses were measured in the serum and vaginal washes, respectively. Serum antibodies predominantly recognized the N‐terminal and basic functional domains of the protein and exhibited neutralizing capacity against Tat‐driven transactivation. Transcutaneous immunization also elicited potent cellular immune responses against Tat and the secretion of high levels of IL‐2, IFN‐γ and IL‐6. These findings demonstrate for the first time that by using a simple and safe immunization procedure, a synthetic Tat protein can elicit potentially protective immune responses. Transcutaneous immunization may be advantageous for the non‐invasive delivery of other HIV candidate vaccine antigens.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

et al. 2004

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“…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 development of humoral 13,14 and Th responses after TCI with proteins or peptides. [15][16][17] Another way of antigen entry through the skin is uptake via noncornified epithelial cells of the HF.…”

mentioning

confidence: 99%

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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“…It is known that antibody levels in the female reproductive tract are regulated by female sex hormones, 17 and in mice, major differences in antibody responses were demonstrated when females were immunized transcutaneously at different stages of the oestrus cycle. 18 Preliminary results from a small number of animals suggest that oestrus cycle differences also occur in the female possum 19 but further studies are needed to obtain more data.…”

Section: Discussionmentioning

confidence: 99%

Mucosal immunity in the brushtail possum (Trichosurus vulpecula): Detection of antibody in serum and at female reproductive sites after intranasal immunization

et al. 2002

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Summary Vaccination strategies for the brushtail possum, which rely upon stimulation of mucosal immunity, are being developed for biocontrol purposes. As little is known about how to stimulate possum immune responses via a mucosal site, groups of possums were immunized intranasally with keyhole limpet haemocyanin (KLH) alone or in combination with known or novel mucosal adjuvants. Antigen-specific antibody titres in female reproductive secretions were measured by ELISA and compared with antibody titres in the serum. Antigen-induced lymphocyte proliferative responses were measured as an indicator of cell-mediated responses. Intranasal immunization with KLH alone stimulated a weak serum antibody response that was significantly increased when KLH was given with cholera toxin subunit B (CTB), recombinant possum tumour necrosis factor α (TNFα) or live Mycobacterium bovis bacillus Calmette Guerin (BCG). Antibody titres in secretions from ovarian follicles and the uterus were very low in animals administered KLH alone. Significantly higher antibody titres to KLH were present in the reproductive secretions of possums immunized with KLH plus CTB, BCG or heat-killed Mycobacterium vaccae. Antibody titres were lower in mucosal secretions than in the serum, but there was a significant correlation between the two. In addition, coadministration of live BCG with KLH produced a strong antigen-specific cell-mediated response to KLH. This study has shown that an immune response to a protein antigen can be stimulated in possums by intranasal immunization and that antigen-specific antibodies can be detected in secretions from the female reproductive tract.

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Transcutaneous immunization induces mucosal and systemic immunity: a potent method for targeting immunity to the female reproductive tract

Cited by 85 publications

References 22 publications

A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

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

Mucosal immunity in the brushtail possum (Trichosurus vulpecula): Detection of antibody in serum and at female reproductive sites after intranasal immunization

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