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

Area of Science:

• Immunology
• Dermatology
• Vaccinology

Background:

• Melanoma vaccines require optimization for improved efficacy.
• Adjuvants like incomplete Freund's adjuvant (IFA) are used to activate dendritic cells (DCs) and modulate the immune response.
• The precise cellular and molecular effects of adjuvants in human skin remain incompletely understood.

Purpose of the Study:

• To investigate the effects of a multipeptide vaccine with IFA on immune cells within human skin.
• To determine the impact of single and repeated vaccinations on dermal dendritic cells and lymphocyte subsets.
• To hypothesize that repeated vaccination might increase regulatory cells.

Main Methods:

• Biopsies were taken from immunization sites of 36 participants during and after 6 weekly immunizations.
• Immunohistochemistry was used to enumerate dendritic cells (DCs) and lymphocyte subsets.
• Cellular localization within skin compartments was characterized at various time points (weeks 0, 1, 3, 7, 12).

Main Results:

• Mature DCs aggregated with lymphocytes around superficial vessels; immature DCs were randomly distributed.
• No significant change in mature DC numbers was observed over time.
• Increases in T and B-cells were noted, with Th2 cells initially outnumbering Th1 lymphocytes (6.6:1 ratio after one vaccine).
• Eosinophils and FoxP3+ cells (regulatory T-cells) accumulated, particularly after three vaccinations, with eosinophils found predominantly in deeper skin layers.

Conclusions:

• The multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which can be reversed with repeated vaccination.
• Repeated vaccination may lead to an increase in FoxP3+ T-cells and eosinophils.
• These findings highlight opportunities for optimizing vaccine regimens and identifying potential monitoring endpoints for new adjuvants.