Dendritic cell activation and functions after mucosal immunization of rhesus macaques with replicating adenovirus-SIV recombinants

Inducing strong mucosal immune responses by vaccination is important for providing protection against Simian Immunodeficiency Virus (SIV). Dendritic cells (DCs) are known to orchestrate effector immune cell responses. Rhesus macaques were immunized mucosally 2 times with replicating adenovirus expressing SIV Env, Gag and Nef (vaccine) or empty adenovirus (control). Rectal biopsies, blood and lymph nodes were collected at 3, 7 and 14 days post-immunization to examine DC subsets and their activation. Plasmacytoid DCs (pDCs, CD123+) and Langerhans cells (LCs, CD11c+CD1ahigh) were significantly increased in the rectal mucosa after the 2nd immunization, however, myeloid DCs (mDCs, CD11c+) were significantly increased in blood. Regardless of DC frequencies, all rectal and blood DC subsets showed up-regulated activation marker expression and enhanced cytokine production. Lymph node DCs did not show any changes in frequencies or activation after the immunizations. There was no significant difference in DC activation between vaccine and control groups which suggested that the DCs quickly recognized the replicating adenovirus vector. Antigen-specific memory T cells were increased in the rectal mucosa after the immunizations and were positively correlated with rectal pDCs and LCs in the vaccine group. The rectal DCs were capable of inducing proliferation of naïve T cells after in vitro co-culture and the vaccine group showed higher T cell proliferation than controls after Env protein stimulation. Our results highlight the rapid response and potential roles of DCs in mucosal immune activation after adenovirus immunizations and identify the initial cellular mechanisms of the adenovirus vaccine regimen in the rhesus macaque model.