期刊
JOURNAL OF CONTROLLED RELEASE
卷 158, 期 2, 页码 240-249出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2011.11.009
关键词
Vaccine delivery; Targeting; Mucosal; Transcytosis; Immunogenicity
资金
- St. George's, University of London
- Bill and Melinda Gates Foundation
- Wellcome Trust, under the Grand Challenges in Global Health Initiative
- Sir Joseph Hotung Trust
The generation of effective immune responses by mucosal vaccination without the use of inflammatory adjuvants, that compromise the epithelial barrier and recruit new cellular targets, is a key goal of vaccines designed to protect against sexually acquired pathogens. In the present study we use a model HIV antigen (CN54gp140) conjugated to transferrin (Tf) and evaluate the ability of the natural transferrin receptor CD71 to modulate immunity. We show that the conjugated transferrin retained high affinity for its receptor and that the conjugate was specifically transported across an epithelial barrier, co-localizing with MHC Class II+ cells in the sub-mucosal stroma. Vaccination studies in mice revealed that the Tf-gp140 conjugate elicited high titres of CN54gp140-specific serum antibodies, equivalent to a systemic vaccination, when conjugate was applied topically to the nasal mucosae whereas gp140 alone was poorly immunogenic. Moreover, the Tf-gp140 conjugate elicited both IgG and IgA responses and significantly higher gp140-specific IgA titre in the female genital tract than unconjugated antigen. These responses were achieved after mucosal application of the conjugated protein alone, in the absence of any pro-inflammatory adjuvant and suggest a potentially useful and novel molecular targeting approach, delivering a vaccine cargo to directly elicit or enhance pathogen-specific mucosal immunity. (C) 2011 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据