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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.


IgA and IgG ASC responses to HA following rAd oral vaccination to either the jejunum or ileum.Results are shown as numbers of HA-specific ASCs/106 PBMC 7 days after vaccination. Each icon represents response level of one subject (A,B). Each bar represents median.
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f2: IgA and IgG ASC responses to HA following rAd oral vaccination to either the jejunum or ileum.Results are shown as numbers of HA-specific ASCs/106 PBMC 7 days after vaccination. Each icon represents response level of one subject (A,B). Each bar represents median.

Mentions: Influenza HA-specific IgG and IgA ASCs were measured in peripheral blood mononuclear cells (PBMCs) on days 0 and 7 after vaccination (Fig. 2). Background ASCs were not detectable on day 0. In the jejunum-targeted release group, a median of 27 IgA ASCs (95 CI: 5–39) and 111 IgG ASCs (95 CI: 3–200) each per 1 × 106 PBMC were found at day 7 with one (IgG) and two (IgA) subjects out of 12 having no detectable ASC response. In the ileum-targeted release group, a median of 54 IgA ASCs (95 CI: 13–146) and 200 IgG ASCs (95 CI: 141–484) each per 1 × 106 PBMC were found at day 7, with 12 out of 12 subjects responding for both IgA and IgG ASCs responses. The number of responders in both IgA and IgG ASCs in the jejunum-targeted group was less than in the ileum-targeted group, but not significantly. The HA-specific IgG ASCs numbers in the ileum-targeted group were significantly different from those in the jejunum-targeted group, but not significantly different in HA-specific IgA ASCs numbers (P = 0.023 (IgG) vs. P = 0.08 (IgA) by Mann-Whitney test).


Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule
IgA and IgG ASC responses to HA following rAd oral vaccination to either the jejunum or ileum.Results are shown as numbers of HA-specific ASCs/106 PBMC 7 days after vaccination. Each icon represents response level of one subject (A,B). Each bar represents median.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: IgA and IgG ASC responses to HA following rAd oral vaccination to either the jejunum or ileum.Results are shown as numbers of HA-specific ASCs/106 PBMC 7 days after vaccination. Each icon represents response level of one subject (A,B). Each bar represents median.
Mentions: Influenza HA-specific IgG and IgA ASCs were measured in peripheral blood mononuclear cells (PBMCs) on days 0 and 7 after vaccination (Fig. 2). Background ASCs were not detectable on day 0. In the jejunum-targeted release group, a median of 27 IgA ASCs (95 CI: 5–39) and 111 IgG ASCs (95 CI: 3–200) each per 1 × 106 PBMC were found at day 7 with one (IgG) and two (IgA) subjects out of 12 having no detectable ASC response. In the ileum-targeted release group, a median of 54 IgA ASCs (95 CI: 13–146) and 200 IgG ASCs (95 CI: 141–484) each per 1 × 106 PBMC were found at day 7, with 12 out of 12 subjects responding for both IgA and IgG ASCs responses. The number of responders in both IgA and IgG ASCs in the jejunum-targeted group was less than in the ileum-targeted group, but not significantly. The HA-specific IgG ASCs numbers in the ileum-targeted group were significantly different from those in the jejunum-targeted group, but not significantly different in HA-specific IgA ASCs numbers (P = 0.023 (IgG) vs. P = 0.08 (IgA) by Mann-Whitney test).

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.