Name
What is the role of Langerhans cells in the human adenovirus-based vaccination process?
Presenter
Elina Gerber-Tichet, Université de Montréal
Co-Author(s)
Gerber-Tichet Elina 1#, Blanchet Fabien 2 & Kremer Eric 1 ; 1Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, 34090 Montpellier, France, 2Institut de Recherche en Infectiologie de Montpellier, CNRS UMR 9004, 34090 Montpellier, France, #Current address: CRCHUM-Centre Hospitalier de l'Université de Montréal, Montréal, H2X0A9
Abstract Category
Fighting & Responding
Abstract
Background: Langerhans cells (LCs) are professional antigen-presenting cells in the epidermis that play a key role in immune surveillance and bridging innate and adaptive immunity. Despite their strategic position, their role in vaccine-induced immune responses remains poorly defined. Human adenoviral vectors (HAdVs), widely used in vaccine development in recent years, as seen during the COVID-19 pandemic, provide a relevant model to investigate LC involvement in vaccination. Methods: Our complementary in vitro model of CD34⁺ LCs derived from umbilical cord blood (CD34-LCs) and ex vivo human skin explants were exposed to non-replicative HAdV-C5, -D26, and -B35 vectors, allowing assessment of vector uptake, cellular activation, and recruitment to the injection site. This dual-model approach provides a comprehensive view of LC responses in controlled and tissue-relevant contexts. Results: CD34-LCs efficiently internalized HAdV vectors, directly or via lactoferrin (Lf), an antimicrobial peptide derived from neutrophils. Exposure triggered secretion of pro-inflammatory and antiviral cytokines and morphological changes indicative of activation. Lf enhanced vector uptake by LCs without thereby increasing the pro-inflammatory or antiviral response. In skin explants, vector injection recruited epidermal LCs (eLCs) to the site and promoted their uptake of viral particles. These results demonstrate a robust functional response of LCs to HAdV vectors, highlighting their key role in the immune response to human adenovirus-based vaccines. Conclusions: Langerhans cells are early contributors to the immune response induced by human adenovirus-based vaccines, providing a basis for strategies to exploit or modulate their activity to enhance vaccine immunogenicity.