4.8 Article

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

Journal

BIOMATERIALS
Volume 35, Issue 27, Pages 7896-7908

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.05.056

Keywords

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

Funding

  1. National Natural Science Foundation of China [81173011]
  2. National Basic Research Program of China (973 program) [2013CB932504]
  3. Science Foundation for Youths of Sichuan Province [2012JQ0024]

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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. (C) 2014 Elsevier Ltd. All rights reserved.

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