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- Title
Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.
- Authors
Zhu, Qing; Talton, James; Zhang, Guofeng; Cunningham, Tshaka; Wang, Zijian; Waters, Robert C; Kirk, James; Eppler, Bärbel; Klinman, Dennis M; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor M; Mumper, Russell J; Berzofsky, Jay A
- Abstract
Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.
- Subjects
GASTROINTESTINAL disease prevention; LARGE intestine; NANOMEDICINE; ORAL vaccines; VAGINAL diseases; RECTAL diseases; MUCOUS membranes; VIRAL vaccines
- Publication
Nature Medicine, 2012, Vol 18, Issue 8, p1291
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.2866