Vaccine strategies utilizing C-type lectin receptors on dendritic cells in vivo

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells capable of initiating and regulating innate and adaptive immunity. The development of effective ways to produce a large number of DCs in laboratories made the use of DCs available in various vaccine approaches. Compared to conventional vaccines, focused on protective antibody responses, DC vaccines emphasize protective T cell immunity but might elicit strong antibody responses as well. In addition, the recent discoveries of functionally distinct DC subsets in various organs and tissues are likely to increase the potential of exploiting DCs in vaccines and immunotherapy. Vaccines composed of DCs generated ex vivo, pulsed with antigens, and matured prior to being re-infused to the body have been widely tried clinically but resulted in limited success due to various obstacles. In this review, new approaches that protein vaccines are selectively targeted to the endocytic C-type lectin receptors on surface of DCs in vivo are discussed.

Keywords: Antigen receptor; C-type lectins; Dendritic cells; Monoclonal antibody.

Fig. 1

Analyses of human immunodeficiency virus Gag proteins expressed from mammalian CHO cells. (A) Soluble, FLAG-tagged Gag p41 and p24 proteins were produced into culture media from the stably transfected CHO cells, followed by anti-FLAG affinity purification. Left panel: Five micrograms each of purified p41 and p24 was subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis with/without (+/-) treatment of β-mercaptoethanol (BME) and boiling at 100℃ for 5 minutes (Boiling). After electrophoresis, the gel was visualized with Coomassie blue stain. Aggregates on the border between stacking and resolving gels and on the bottom of loading wells are detected from the purified p41 without BME & Boiling. Right panel: Zero point five microgram each of purified p41 and p24 was subjected to SDS-polyacrylamide gel electrophoresis with/without BME & Boiling. After electrophoresis, the gel was transferred onto polyvinylidene difluoride (PVDF) membrane, blotted with anti-Gag antibody, and visualized with chemiluminescent reagent. Aggregates with high molecular weight are detected from the purified p41 without BME & Boiling. (B) Culture supernatants from stably transfected CHO cells expressing soluble, FLAG-tagged Gag p41 and p24 proteins were analyzed. Five microliters each of cell culture supernatants was subjected to SDS-polyacrylamide gel electrophoresis with/without BME & Boiling. After electrophoresis, the gel was transferred onto PVDF membrane, blotted with anti-Gag antibody, and visualized with chemiluminescent reagent. Aggregates with high molecular weight are detected from the cell culture supernatant of p41 without BME & Boiling.