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Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells
Igor M. Belyakov, … , Gregory M. Glenn, Jay A. Berzofsky
Igor M. Belyakov, … , Gregory M. Glenn, Jay A. Berzofsky
Published April 1, 2004
Citation Information: J Clin Invest. 2004;113(7):998-1007. https://doi.org/10.1172/JCI20261.
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Article AIDS/HIV

Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells

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Abstract

Transcutaneous immunization (TCI), the application of vaccines on the skin, induces robust systemic and mucosal antibodies in animal models and in humans. The means by which mucosal immune responses to vaccine antigens are elicited by TCI has not been well characterized. We examined the effect of TCI with an HIV peptide vaccine on the induction of mucosal and systemic CTL responses and protective immunity against mucosal challenge with live virus in mice. Robust HIV-specific CTL responses in the spleen and in the gut mucosa were detected after TCI. The responses were dependent upon the addition of an adjuvant and resulted in protection against mucosal challenge with recombinant vaccinia virus encoding HIV gp160. Although it is clear that adjuvant-activated DCs migrated mainly to draining lymph nodes, coculture with specific T cells and flow cytometry studies with DCs isolated from Peyer’s patches after TCI suggested that activated DCs carrying skin-derived antigen also migrated from the skin to immune-inductive sites in gut mucosa and presented antigen directly to resident lymphocytes. These results and previous clinical trial results support the observation that TCI is a safe and effective strategy for inducing strong mucosal antibody and CTL responses.

Authors

Igor M. Belyakov, Scott A. Hammond, Jeffrey D. Ahlers, Gregory M. Glenn, Jay A. Berzofsky

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Figure 8

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APCs in the PPs contain skin-derived fluorescent LT after TCI. (A–F) BAL...
APCs in the PPs contain skin-derived fluorescent LT after TCI. (A–F) BALB/c mice were left untreated (A and D) or were immunized with 50 μg of Alexa Fluor 488–conjugated LT (AF-LT; B, C, E, and F). Forty-eight hours later, inguinal LNs and PPs were isolated and analyzed for cell populations containing AF-LT (A, B, D, and E). The CD11c, MHC class II (H-2 I-Ad) surface expression of AF-LT–positive cells was determined for both inguinal LN (C) and PP (F) cells. Similar results were observed 24 hours after application of AF-LT. The percent of AF-LT–positive cells are listed in A, B, D, and E. The percent of cells present in each quadrant are listed in C and F.

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