Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo

Nina Salabert, Biliana Todorova, Frédéric Martinon, Raphaël Boisgard, Gerard Zurawski, Sandra Zurawski, Nathalie Dereuddre-Bosquet, Antonio Cosma, Thierry Kortulewski, Jacques Banchereau, Yves Levy, Roger Le Grand, Catherine Chapon*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR-7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848.

Original languageEnglish
Pages (from-to)689-700
Number of pages12
JournalEuropean Journal of Immunology
Volume46
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016
Externally publishedYes

Keywords

  • Fluorescence imaging
  • Langerhans cell
  • Nonhuman primate
  • Skin
  • Vaccination

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