Adenoviral vectors coated with cationic PEG derivatives for intravaginal vaccination against HIV-1

作者：Xie, Zhaolu; Ji, Zhonghua; Zhang, Zhirong; Gong, Tao; Sun, Xun^*

来源：Biomaterials, 2014, 35(27): 7896-7908.

DOI：10.1016/j.biomaterials.2014.05.056

• Adenovirus
• Cationic PEG derivative
• Intravaginal immunization
• Mucus
• Immune response

Mucus layer coating the vaginal epithelium represents a barrier for intravaginally delivered recombined adenoviral (rAd) vectors, but it could be overcome by proper polyethylene glycol (PEG) modification. Here we synthesized two cationic PEG derivatives, amino-(EO)(n)/(AGE)(m)-Cyss (APCs). The polymers contained neutral linear PEG (2-5 kDa) to provide a hydrophilic surface and amine pendants to provide positive charge for coating negatively charged rAd by physical adsorption. Given proper molecular composition, the polymer (5k-APC) could coat rAd without causing aggregation, facilitating its mucus penetrating ability and enhancing gene expression both in vitro and in vivo. With HIVgag as the model antigen, the polymer-rAd complexes were administered intravaginally to elicit both systemic and mucosal immune responses. 5k-APC-rAd immunization elicited robust HIVgag-specific cellular responses and also induced higher antigen-specific serum IgG. More importantly, mice immunized with 5k-APC-rAd showed higher level of IgA in vaginal lavage fluid. These findings suggest that 5k-APC-rAd is a promising system for intravaginal immunization against infectious diseases such as HIV within the vaginal tract.

• 出版日期2014-9
• 单位四川大学