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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

Fold increases in the anti-HA IgA responses to influenza HA following vaccine delivery by RCC to either the jejunum or ileum.Data are shown when a > 2-fold increase in GMT from day 0 to day 28 nasal and fecal samples had occurred.
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f4: Fold increases in the anti-HA IgA responses to influenza HA following vaccine delivery by RCC to either the jejunum or ileum.Data are shown when a > 2-fold increase in GMT from day 0 to day 28 nasal and fecal samples had occurred.

Mentions: Nasal wash and fecal samples were collected from human volunteers in this study. Total IgA was quantified by ELISA in order to normalize for yield. Following normalization, the fold rise in HA-specific IgA antibody titers was measured pre and post immunization. The background was high in both samples; slightly higher with nasal samples than fecal samples, but several subjects had a detectable specific IgA increase in titer post immunization. The number of subjects with detectable increases in anti-HA IgA titers (either in fecal or nasal IgA) was nine out of twelve in the ileum-targeted group and ten out of twelve in the jejunum-targeted group. Six subjects had increases in HA-specific IgA titers in nasal wash samples post-immunization in the jejunum group and four subjects had detectable IgA nasal responses in the ileum-targeted group (Fig. 4). The magnitudes were similar between groups. Four and five subjects had detectable increases in HA-specific IgA in fecal samples in the jejunum and ileum-targeted group, respectively, with a slightly higher response in the ileum delivery group (Fig. 4).


Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule
Fold increases in the anti-HA IgA responses to influenza HA following vaccine delivery by RCC to either the jejunum or ileum.Data are shown when a > 2-fold increase in GMT from day 0 to day 28 nasal and fecal samples had occurred.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Fold increases in the anti-HA IgA responses to influenza HA following vaccine delivery by RCC to either the jejunum or ileum.Data are shown when a > 2-fold increase in GMT from day 0 to day 28 nasal and fecal samples had occurred.
Mentions: Nasal wash and fecal samples were collected from human volunteers in this study. Total IgA was quantified by ELISA in order to normalize for yield. Following normalization, the fold rise in HA-specific IgA antibody titers was measured pre and post immunization. The background was high in both samples; slightly higher with nasal samples than fecal samples, but several subjects had a detectable specific IgA increase in titer post immunization. The number of subjects with detectable increases in anti-HA IgA titers (either in fecal or nasal IgA) was nine out of twelve in the ileum-targeted group and ten out of twelve in the jejunum-targeted group. Six subjects had increases in HA-specific IgA titers in nasal wash samples post-immunization in the jejunum group and four subjects had detectable IgA nasal responses in the ileum-targeted group (Fig. 4). The magnitudes were similar between groups. Four and five subjects had detectable increases in HA-specific IgA in fecal samples in the jejunum and ileum-targeted group, respectively, with a slightly higher response in the ileum delivery group (Fig. 4).

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