Yuhong Jiang1, Man Li, Zhirong Zhang, Tao Gong, Xun Sun. 1. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China.
Abstract
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 CD8(+)T and IL-4 positive CD4(+)T cells, indicating high cellular immune responses. This vaccine candidate also led to strong humoral immune responses (IgG/IgG1/IgG2a) with balanced Th1/Th2 CD4(+)T 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.
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 CD8(+)T and IL-4 positive CD4(+)T cells, indicating high cellular immune responses. This vaccine candidate also led to strong humoral immune responses (IgG/IgG1/IgG2a) with balanced Th1/Th2 CD4(+)T 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.
Authors: William M Gwinn; Shaun M Kirwan; Sheena H Wang; Kathleen A Ashcraft; Neil L Sparks; Catherine R Doil; Tom G Tlusty; Leslie S Casey; Susan K Hollingshead; David E Briles; Richard S Dondero; Anthony J Hickey; W Michael Foster; Herman F Staats Journal: Vaccine Date: 2010-08-17 Impact factor: 3.641
Authors: J E Schmitz; M J Kuroda; S Santra; V G Sasseville; M A Simon; M A Lifton; P Racz; K Tenner-Racz; M Dalesandro; B J Scallon; J Ghrayeb; M A Forman; D C Montefiori; E P Rieber; N L Letvin; K A Reimann Journal: Science Date: 1999-02-05 Impact factor: 47.728
Authors: Victor C Huber; Raelene M McKeon; Martha N Brackin; Laura A Miller; Rachael Keating; Scott A Brown; Natalia Makarova; Daniel R Perez; Gene H Macdonald; Jonathan A McCullers Journal: Clin Vaccine Immunol Date: 2006-09
Authors: Danilo R Casimiro; Ling Chen; Tong-Ming Fu; Robert K Evans; Michael J Caulfield; Mary-Ellen Davies; Aimin Tang; Minchun Chen; Lingyi Huang; Virginia Harris; Daniel C Freed; Keith A Wilson; Sheri Dubey; De-Min Zhu; Denise Nawrocki; Henryk Mach; Robert Troutman; Lynne Isopi; Donna Williams; William Hurni; Zheng Xu; Jeffrey G Smith; Su Wang; Xu Liu; Liming Guan; Romnie Long; Wendy Trigona; Gwendolyn J Heidecker; Helen C Perry; Natasha Persaud; Timothy J Toner; Qin Su; Xiaoping Liang; Rima Youil; Michael Chastain; Andrew J Bett; David B Volkin; Emilio A Emini; John W Shiver Journal: J Virol Date: 2003-06 Impact factor: 5.103