Enhancement of Nasal HIV Vaccination with Adenoviral Vector-Based Nanocomplexes Using Mucoadhesive and DC-Targeting Adjuvants.

Purpose: To investigate the vaccine effect of a replication-defective recombinant adenovirus 5 (rAd5)-based nanocomplex with chitooligosaccharides (Oligo) and mannosylated polyethyleneimine-triethyleneglycol (mPEI) as adjuvants for human immunodeficiency virus (HIV) infection. Methods: Physical characteristics were determined through detecting the size, zeta potential and morphology of Oligo-mPEI-rAd5 nanocomplex, and in vitro vaccine uptake and transduction efficiency were estimated. Nanocomplexes were then administered intranasally to Balb/c mice to evaluate in vivo rAd5 residence in nasal cavity and HIVgag-specific immune responses using cytotoxic T lymphocyte (CTL), intracellular cytokine staining (ICS) and ELISA assay. Results: The mucoadhesivity of Oligo prolonged nasal residence time, while the dendritic cell (DC) specificity of mPEI improved vaccine uptake. These two adjuvants jointly enhanced transduction efficiency of rAd5. Oligo-mPEI-rAd5 nanocomplex elicited potent HIVgag-specific CTL response and increased IFN-γ positive CD8T and IL-4 positive CD4T cells, indicating high cellular immune responses. This vaccine candidate also led to strong humoral immune responses (IgG/IgG1/IgG2a) with balanced Th1/Th2 CD4T cell activity. Moreover, mice nasally immunized with Oligo-mPEI-rAd5 showed higher levels of SIgA in nasal washes than did mice immunized with rAd5. Conclusions: Intranasal delivery of Oligo-mPEI-rAd5 with a prime-boost regimen is a potential immunization for HIV infection, inducing HIVgag-specific cellular, humoral and mucosal immune responses. [ABSTRACT FROM AUTHOR]