Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule

被引:43
作者
Kim, Leesun [1 ]
Martinez, C. Josefina [1 ]
Hodgson, Katie A. [1 ]
Trager, George R. [1 ]
Brandl, Jennifer R. [1 ]
Sandefer, Erik P. [2 ]
Doll, Walter J. [2 ]
Liebowitz, Dave [1 ]
Tucker, Sean N. [1 ]
机构
[1] Vaxart Inc, 385 Oyster Point 9A, San Francisco, CA 94080 USA
[2] Scintipharma, 2201 Regency Rd 403, Lexington, KY 40503 USA
关键词
PEYERS-PATCHES; AVIAN INFLUENZA; HOMING RECEPTOR; IGA; MEMORY; CELLS;
D O I
10.1038/srep37295
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
There are several benefits of oral immunization including the ability to elicit mucosal immune responses that may protect against pathogens that invade through a mucosal surface. Our understanding of human immune biology is hampered by the difficulty in isolating mucosal cells from humans, and the fact that animal models may or may not completely mirror human intestinal immunobiology. In this human pharmacodynamic study, a novel adenovirus vector-based platform expressing influenza hemagglutinin was explored. We used radio-controlled capsules to deliver the vaccine to either the jejunum or the ileum. The resulting immune responses induced by immunization at each of the intestinal sites were investigated. Both intestinal sites were capable of inducing mucosal and systemic immune responses to influenza hemagglutinin, but ileum delivery induced higher numbers of antibody secreting cells of IgG and IgA isotypes, increased mucosal homing B cells, and higher number of vaccine responders. Overall, these data provided substantial insights into human mucosal inductive sites, and aided in the design and selection of indications that could be used with this oral vaccine platform.
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页数:11
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