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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2010

Open Access 01-12-2010 | Research

Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis

Authors: Jochen T Schaefer, James W Patterson, Donna H Deacon, Mark E Smolkin, Gina R Petroni, Emily M Jackson, Craig L Slingluff Jr

Published in: Journal of Translational Medicine | Issue 1/2010

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Abstract

Background

Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs) and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA) would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells.

Methods

During and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments.

Results

Mature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3+ cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers.

Conclusions

A multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3+T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants.

Trail Registration

ClinicalTrials.gov Identifier: NCT00705640
Appendix
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Metadata
Title
Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis
Authors
Jochen T Schaefer
James W Patterson
Donna H Deacon
Mark E Smolkin
Gina R Petroni
Emily M Jackson
Craig L Slingluff Jr
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2010
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-8-79

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