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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 5

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TCI generated CTL responses in the PPs, SP, and lung. BALB/c mice (n = 5...
TCI generated CTL responses in the PPs, SP, and lung. BALB/c mice (n = 5) were immunized twice 2 weeks apart with 50 μg PCLUS3-IIIB peptide, 10 μg CT, and 50 μg CpG by the indicated route of administration for each group as follows: group 1, transcutaneous prime and intrarectal boost; group 2, transcutaneous prime and boost; group 3, subcutaneous (SC) prime and intrarectal boost; group 4, intraperitoneal (IP) prime (peptide and CpG given intraperitoneally and CT administered intrarectally because CT is toxic given intraperitoneally) and intrarectal boost; group 5, intrarectal prime and intrarectal boost; and group 6, no treatment during the first immunization and an intrarectal immunization at the second immunization interval (Single IR). Four weeks after the final immunization, PPs (A), SP (B), and lung (C) were removed, processed, stimulated in vitro with P18-I10 peptide (1 μM) for 7 days, and assayed for cytolytic activity in a 51Cr-release assay.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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