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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Scintigraphy visualization of subjects given vaccine released in the upper small intestine (A) versus the lower small intestine (B). Each subject swallows vaccine in a size 000 mechanical capsule loaded with liquid vaccine and a radiolabeled tracer. Post dose, one can visualize the capsule transiting through the stomach (Stom, red circle) and the intestine as a discrete spot because the radiolabeled tracer is all contained with the capsule. As the radiolabeled tracer proceeds through the proximal small intestine (PSI, purple circle) and the distal small intestine (DSI, yellow circle), the figures are labeled with such. Post release, the liquid contents are ejected from the capsule and dispersion of the material can be visualized as it spreads away from the capsule. When verified that the dispersed material has reached the colon (Colon, green outlined region), scintigraphy visualization is no longer required.
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f1: Scintigraphy visualization of subjects given vaccine released in the upper small intestine (A) versus the lower small intestine (B). Each subject swallows vaccine in a size 000 mechanical capsule loaded with liquid vaccine and a radiolabeled tracer. Post dose, one can visualize the capsule transiting through the stomach (Stom, red circle) and the intestine as a discrete spot because the radiolabeled tracer is all contained with the capsule. As the radiolabeled tracer proceeds through the proximal small intestine (PSI, purple circle) and the distal small intestine (DSI, yellow circle), the figures are labeled with such. Post release, the liquid contents are ejected from the capsule and dispersion of the material can be visualized as it spreads away from the capsule. When verified that the dispersed material has reached the colon (Colon, green outlined region), scintigraphy visualization is no longer required.

Mentions: Twenty-four subjects were randomly assigned to receive the vaccine delivered to either the ileum or jejunum. Subjects were enrolled, fasted overnight, and given a liquid formulation of vaccine with a radioactive tracer in the mechanical capsule. The vaccine capsule’s progress through the digestive tract was monitored by gamma scintigraphy, and the capsule contents were released in the upper small intestine (jejunum) or lower small intestine (ileum) by radio signal that triggered the liquid contents to be ejected out of the capsule. Release was confirmed by scintigraphy; dispersion of the radioactive tracer demonstrated content release. Confirmed delivery to the ileum or jejunum occurred in 24 subjects out of 25 attempted. The subject with poor delivery had the contents of the RCC released in the colon or rectum, and was replaced such that 24 total subjects were monitored for immune responses. A representative figure showing the tracking of the capsule, followed by release in the ileum and jejunum are shown (Fig. 1).


Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule
Scintigraphy visualization of subjects given vaccine released in the upper small intestine (A) versus the lower small intestine (B). Each subject swallows vaccine in a size 000 mechanical capsule loaded with liquid vaccine and a radiolabeled tracer. Post dose, one can visualize the capsule transiting through the stomach (Stom, red circle) and the intestine as a discrete spot because the radiolabeled tracer is all contained with the capsule. As the radiolabeled tracer proceeds through the proximal small intestine (PSI, purple circle) and the distal small intestine (DSI, yellow circle), the figures are labeled with such. Post release, the liquid contents are ejected from the capsule and dispersion of the material can be visualized as it spreads away from the capsule. When verified that the dispersed material has reached the colon (Colon, green outlined region), scintigraphy visualization is no longer required.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121599&req=5

f1: Scintigraphy visualization of subjects given vaccine released in the upper small intestine (A) versus the lower small intestine (B). Each subject swallows vaccine in a size 000 mechanical capsule loaded with liquid vaccine and a radiolabeled tracer. Post dose, one can visualize the capsule transiting through the stomach (Stom, red circle) and the intestine as a discrete spot because the radiolabeled tracer is all contained with the capsule. As the radiolabeled tracer proceeds through the proximal small intestine (PSI, purple circle) and the distal small intestine (DSI, yellow circle), the figures are labeled with such. Post release, the liquid contents are ejected from the capsule and dispersion of the material can be visualized as it spreads away from the capsule. When verified that the dispersed material has reached the colon (Colon, green outlined region), scintigraphy visualization is no longer required.
Mentions: Twenty-four subjects were randomly assigned to receive the vaccine delivered to either the ileum or jejunum. Subjects were enrolled, fasted overnight, and given a liquid formulation of vaccine with a radioactive tracer in the mechanical capsule. The vaccine capsule’s progress through the digestive tract was monitored by gamma scintigraphy, and the capsule contents were released in the upper small intestine (jejunum) or lower small intestine (ileum) by radio signal that triggered the liquid contents to be ejected out of the capsule. Release was confirmed by scintigraphy; dispersion of the radioactive tracer demonstrated content release. Confirmed delivery to the ileum or jejunum occurred in 24 subjects out of 25 attempted. The subject with poor delivery had the contents of the RCC released in the colon or rectum, and was replaced such that 24 total subjects were monitored for immune responses. A representative figure showing the tracking of the capsule, followed by release in the ileum and jejunum are shown (Fig. 1).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus