Abstract:
: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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Xie Z,Ji Z,Zhang Z,Gong T,Sun Xdoi
10.1016/j.biomaterials.2014.05.056subject
Has Abstractpub_date
2014-09-01 00:00:00pages
7896-908issue
27eissn
0142-9612issn
1878-5905pii
S0142-9612(14)00613-9journal_volume
35pub_type
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